Download Bioinspirations: Cell-Inspired Small-Scale

Integrative and Comparative Biology, volume 51, number 1, pp. 133–141
doi:10.1093/icb/icr010
SYMPOSIUM
Bioinspirations: Cell-Inspired Small-Scale Systems for Enabling
Studies in Experimental Biomechanics
Warren C. Ruder1,* and Philip R. LeDuc2,*,†,‡,§
*Department of Biomedical Engineering, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, PA 15213, USA;
†
Department of Mechanical Engineering, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, PA 15213, USA;
‡
Department of Computational Biology, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, PA 15213, USA;
§
Department of Biological Sciences, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, PA 15213, USA
From the symposium ‘‘Bioinspiration: Applying Mechanical Design to Experimental Biology’’ presented at the annual
meeting of the Society for Integrative and Comparative Biology, January 3–7, 2011, in Salt Lake City, Utah.
1
2
E-mail: [email protected]
E-mail: [email protected]
Synopsis Biomechanical forces govern the behaviors of organisms and their environment and examining these behaviors
to understand the underlying phenomena is an important challenge. One experimental approach for probing these
interactions between organisms and their biomechanical environment uses biologically-inspired, artificial surrogates
that reproduce organic mechanical systems. For the case of complex, multicellular organisms, robot surrogates have
been particularly effective, such as in the analysis of the fins of fish and insects’ wings. This biologically-inspired approach
is also exciting when examining cell-scale responses as multicellular organisms’ behavior is directly influenced by the
integrated interactions of smaller-scale components (i.e., cells). In this review, we introduce the burgeoning field of
engineering of artificial cells, which focuses on developing cell-scale entities replicating cellular behaviors. We describe
both a bottom-up approach to constructing artificial cells, using molecular components to directly assemble artificial
cells, as well as a top-down approach, in which living cells are encapsulated in a single entity whose behavior is determined by its constituent members. In particular, we discuss the potential role of these artificial cells as implantable
controllers, designed to alter the mechanical behavior of a host organism. Eventually, artificial cells designed to function
as small-scale controllers may help alter organisms’ phenotypes.
Introduction
The complex interplay between physical forces driving ecological systems and organisms affects problems throughout comparative biology. In particular,
mechanical forces are often of interest because they
play a significant role, both in defining the internal
physiology and the morphology of individual organisms, as well as shaping their terrestrial or aquatic
environments. Biomechanics plays an important roll
at all scales of biology, from molecules and tissues to
organisms, communities, and ecosystems, especially
in comparative studies. The study of comparative
biomechanics has been enhanced further by the
biologically-inspired approach, in which mechanical
devices that recreate the physical structures and
movements of complex eukaryotes are used to examine the specific mechanical phenomena affecting an
organism, by enabling detailed, robust, and repeatable experiments. For example, for the complex motions of animals, biorobotic surrogates have been
developed that reproduce the kinematics of structures ranging from wings to fins (Long et al. 2006;
Lauder et al. 2007; Shang et al. 2009). These systems
are especially useful because they spare the actual
organisms from harm during experiments, while
allowing the controlled actuation of biomechanical
structures in a manner programmed by the
experimentalist.
Advanced Access publication May 5, 2011
ß The Author 2011. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved.
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134
While these multicellular organisms exhibit complex mechanical structures, morphologies, and movements, cellular processes regulate their underlying
physiology. Cellular biomechanics focuses on understanding the cell’s ability to interpret and respond to
mechanical cues in the cell’s local environment
(Janmey and McCulloch 2007). Understanding
these small-scale biomechanics can also be accomplished through the application of biologicallyinspired approaches (Zhang et al. 2007). Just as
robotic surrogates can be developed for larger organisms, artificial surrogates can be developed for individual cells. The development of artificial cells
presents an important challenge, and steady progress
is being made to develop small-scale artificial systems
that mimic important cellular functions (LeDuc et al.
2007; Zhang et al. 2008).
In this review, we introduce advances and
approaches in the engineering of artificial cells, including the potential role of artificial cells in examining comparative biomechanics. We describe cells
and their artificial surrogates as controllers embedded in their environment, with the capability of
perturbing a single node in a network of biological
interactions. These perturbations can have longlasting, broad effects in a tissue or a host organism
and therefore potentially can manipulate the organism’s behavior. While this ability of artificial cells to
regulate their extracellular environment has traditionally been developed with medical applications
in mind (Lim and Sun 1980; Lohr et al. 2001;
Desai 2002; Orive et al. 2003), we devote this
review to exploring artificial cells in the context of
how their abilities might be extended to modulate
the physiology of animals for comparative studies
in biomechanics. Next, we introduce the field of cellular mechanics, with a focus on cellular mechanotransduction, the process whereby a cell integrates its
internal biochemical signal transduction with its response to mechanical stress (Vogel 2006; Vogel and
Sheetz 2006; Janmey and McCulloch 2007). In order
to engineer these abilities in biologically-inspired artificial systems, we describe two general approaches
for designing and constructing artificial cells. We
then describe recent work geared toward developing
artificial analogs to the mechanical components and
behaviors of living cells, including work to create
artificial internal structures and work to develop artificial cell motility. Next, we discuss potential strategies for uptake and release of environmental
components and conclude with a discussion about
how internal signaling circuits may be embedded in
artificial cells.
W. C. Ruder and P. R. LeDuc
Inspiration from control systems for engineered
mechanical systems
Ultimately, we envision artificial cells as implantable
controllers of their environment, capable of interacting with a host organism’s physiology, and evoking
mechanical behaviors for studies in comparative biomechanics. Just as control modules form the computational command center for robots, biological
organisms contain control modules enabling highly
sophisticated behaviors including mechanical movement. As a result, biological organisms have inspired
the design of robots, especially for the study of comparative biomechanics (Long et al. 2006; Lauder et al.
2007; Shang et al. 2009). These robotic devices have a
number of advantages over studying an organism’s
biomechanical components directly, including the
ability to manipulate a mechanical system, such as
a wing or a fin, at specific times with specific frequencies. Linkages within a mechanical system
can be removed, allowing a reductionist approach
to be used to understand how a system of components works together. Central to each of these is
the control module that allows for specific movements to be generated in a precise fashion. Just
as robotic, biomechanical surrogates are extremely
successful for investigating the mechanics of multicellular organisms, the robot-organism, biologicallyinspired approach can be extended to create artificial surrogates for unicellular organisms and
single cells as well (LeDuc et al. 2007, Zhang et al.
2008).
Cellular mechanics and mechanotransduction
The small-scale study of the mechanical functions of
single cells is broadly encompassed by the field of
cellular biomechanics, and like the study of mechanical systems at larger scales, its subfields are concerned with common mechanical behaviors and
functions (Janmey and McCulloch 2007). While
many subfields exist, four familiar areas include:
(1) mechanical properties, (2) mechanical actuators,
(3) motility, and (4) mechanotransduction. The first
three of these are largely self-explanatory, while the
fourth requires an exploration of slightly more abstraction. We will describe this last area—mechanotransduction—as particularly important when
understanding the control of bioinspired mechanical
systems at small scales. The first three areas of cellular mechanics—mechanical properties, mechanical
actuators, and motility—focus on an investigation of
how forces are supported and manipulated by cells
to their advantage. Many of the first studies of cellular biomechanics focused on cellular mechanical
Artificial cells in biomechanics
properties, which can be defined as the relationship
between force and displacement (or, alternatively,
stress and strain) in a material. Extensive studies
have been conducted that examine this mechanical
stress–strain relationship in a range of cellular materials and macromolecules including those that compose cell membranes, cell walls, and the cell’s internal
mechanical scaffold, the cytoskeleton. These studies
have been performed in various environments, under
compressive, tensile, or shear force (Janmey and
McCulloch 2007). Furthermore, the study of cellular
actuators has examined components of structures
such as flagella, cilia, and pseudopodia in order to
understand how systems of these components work
together to form a single actuator. The complex behavior of groups of these actuators, generally for the
purpose of cellular propulsion, is studied in cellular
motility. While cells can swim in liquid environments, the locomotion of cells as they crawl through
masses, such as cells migrating through tissue during
embryogenesis or metastasis of tumors is an equally
expansive field.
While studies in cellular material properties,
actuators, and motility clearly examine the actual
mechanical systems, studies in cellular mechanotransduction are concerned with internal cell signaling. Mechanotransduction, the ability of cells to
sense, generate, and respond to external forces, involves a diverse range of biochemical and structural
changes within the cell (Vogel and Sheetz 2006).
Sensing mechanical stimulation and related responses
involve a complex set of molecular interactions that
can lead to seemingly contradictory results (Niklason
et al. 1999). Mechanical stimulation of eukaryotic
cells has produced a wide-range of effects in the proteome, including mitogen-activated protein (MAP)
kinase upregulation (Shrode et al. 1997; Li et al.
1999; Ferrer et al. 2001; Bellin et al. 2009), and in
gene expression profiles (Resnick et al. 1997; Topper
and Gimbrone 1999; Garcia-Cardena et al. 2001).
Much research on this mechanical–chemical link
has focused on the cytoskeleton (Vogel and Sheetz
2006) and its connection to the extracellular matrix
(ECM) (Griffith and Swartz 2006). Eukaryotic cells
are known to be significantly influenced by the cytoskeleton filament system (Vogel and Sheetz 2006).
This complex, highly organized structure, plays a
major role in cells’ shapes as well as in motility, division, and polarity (Griffith and Swartz 2006; Vogel
and Sheetz 2006; Janmey and McCulloch 2007). An
important area of research is the manner in which
extracellular forces are transmitted into cells. Much
of this research focuses on one of these links—the
focal adhesion complex—a heterocomplex of
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proteins including transmembrane integrins, syndecans, paxillin, vinculin, and talin. These complexes
connect the actin cytoskeleton to the ECM, linking
the extracellular mechanical environment to the intracellular architecture. These complexes can be
probed through molecular interactions with specific
cell-surface receptors, such as integrins and
syndecans, which bind to extracellular adhesion molecules. These receptors can activate intracellular signaling pathways to control cell structure and
function (Plopper and Ingber 1993; Wang et al.
1993; Wang and Ingber 1994; Alenghat et al. 2000;
Bellin et al. 2009). One of the key underlying
elements is the role of these structural cellular components, the focal adhesion complexes, and the
cytoskeleton
as
mechanical
stress
sensors.
Mechanical loads on these structures catalyze phosphorylation of proteins participating in cell signaling
and this force is transmitted directly to the cell’s
nucleus as well, both of which serve as important
inputs into the cell’s own control architecture
(Vogel and Sheetz 2006). The cell can then take
these inputs and integrate them with other intracellular signals and remodel its phenotype—such as
choosing to upregulate the expression of proteins,
potentially altering its mechanical phenotype.
Alternatively, cells can respond by remodeling their
extracellular matrix by changing the composition and
abundance of extracellular matrix proteins-like collagen and elastin–potentially to shore up these structures against increased forces. This leads directly to a
phenotypic change in the composition of tissues, and
potentially a functional change in the mechanical behavior of an organism’s tissue (Griffith and Swartz
2006).
This process of translating the mechanical environment into phenotypic choice is clearly a result
of the cell’s ability to function as a control module
for its mechanical environment. Similarly, developing
artificial surrogates at the cellular scale could be important and potentially used as controllers of local
(tissue) and global (organism) phenotype and behavior (LeDuc et al. 2007; Zhang et al. 2008). For experimental studies, these controllers could potentially
serve as modulators of behavior, allowing individual
mechanical behaviors to be triggered in a more precise manner in living organisms. This proposed
model of artificial cells as controllers of local behavior is shown in Fig. 1. In the figure, an artificial cell,
consisting of a synthetic liposome containing different chemical products, is able to both interpret and
respond to the local environment in a multicellular
organism.
136
Fig. 1 Biologically-inspired artificial cells as host controllers.
Artificial cell engineering is a developing field that aims to create
synthetic constructs capable of interacting dynamically with a host
organism. Here, we show the potential response and regulation
of mechanical stress in a host’s tissue by a proposed artificial cell
acting as a mechanical control module. The artificial cell is made
of a synthetic liposome containing different molecules that
dynamically react. It detects environmental mechanical stress and
upregulates the stress by releasing stimulants, evoking contraction
in the host’s tissue in a potential positive-feedback loop.
Artificial cells: building small-scale synthetic
surrogates
In this review, we propose two main frameworks for
constructing artificial cells that we describe as
‘‘bottom-up’’ and ‘‘top-down.’’ For artificial cells, it
is important to define their particular contents, as
this will give rise to their behavior, as well as their
encapsulation system, the latter of which must be
tailored to the particular contents. We previously
described two general approaches for the construction of artificial cells (Zhang et al. 2008) and they
remain useful in understanding options for constructing synthetic surrogates. The first approach,
which can be termed ‘‘bottom-up,’’ seeks to construct artificial cells by encapsulating an assembly
of molecular components that are designed to work
together to mimic simple behaviors of cells such as
the timed release of ligands, which activate living
cells in the local tissue environment. The second,
‘‘top-down’’ approach in artificial cell engineering
takes combinations of living cells and encapsulates
them in a single entity, in which the behavior of
the construct is determined by the choice of cell
types to include in the encapsulation. This top-down
approach for creating an artificial cell stands apart
from the synthetic biology method described by
J. Craig Venter’s team and their recent insertion of
W. C. Ruder and P. R. LeDuc
a completely synthetic Mycoplasma mycoides genome
into M. capricolum to reboot the latter as new
M. mycoides (Gibson et al. 2010). The two approaches
we describe in this review are detailed in Fig. 2.
Examples of encapsulation systems include liposomes
or hydrogels, for the bottom-up and top-down
approaches, respectively. By choosing encapsulation
materials tailored to the location in an organism
where artificial cells will serve, artificial cells could be
tailored to be effective implantable controllers.
For the bottom-up approach, if more than one set
of molecular interactions is to be included in a single
cell for greater behavioral complexity, compartmentation of the reactions within the cell can be utilized
(Long et al. 2005; Noireaux et al. 2005). It is important to note that membrane-bounded compartments
(e.g., liposomes) that are passive—and simply release
a single drug over time—are not generally considered
artificial cells. However, once a number of components are interacting together to simulate some type
of cellular behavior, such as sensing the cell’s environment or changing its internal mechanical properties dynamically, the system can begin to be
considered an artificial cell. For example, in one potential bottom-up approach to an artificial cell, a
synthetic construct could be used as an experimental
model for cytoplasmic organization. Distribution of
protein could then be controlled through microcompartmentation, whereby proteins are enclosed in different liposomal systems, as shown in Fig. 3. The
liposomes could consist of two immiscible aqueous
solutions and the partition between the two phases
results in microcompartmentation. It has been
shown that this compartmentation and associated
protein interactions can be modified into a single
phase through altering the temperature or osmolarity
(Long et al. 2005). As the order of the complexity of
the components expands, the relative level of behaviors could be tailored to a particular environment.
Ideally, the artificial construct would be inspired by
the control system of actual cells—genetic regulatory
networks. One example of a potentially complex artificial cell would contain a type of pseudotranslation machinery within an encapsulated
system. This system would utilize artificial genetic
circuits that mimic the type found in natural cells
(Noireaux et al. 2005).
For a top-down approach, artificial cells can be
constructed by packaging groups of cells as a single
entity within an encapsulation, with the goal of
achieving specified complex behaviors. From a
human therapeutic perspective, a number of systems
have been proposed that take advantage of the
top-down approach we describe in this review
137
Artificial cells in biomechanics
Fig. 2 Approaches for constructing artificial cells. Artificial cells
can be constructed with both bottom-up (A) and top-down
(B) approaches (Zhang et al. 2008). For bottom-up construction,
chemicals that react dynamically in potentially complex ways are
encapsulated in a synthetic liposome—i.e., a lipid bilayer.
Alternatively, for top-down construction, combinations of living
cells are encapsulated in a system such as a cross-linked hydrogel.
The single entity—the encapsulation and its constituent living
members—is then defined as an artificial cell.
(Lohr et al. 2001; Desai 2002; Orive et al. 2003), but
the advantages are equally relevant when considering
artificial cells as implantable controllers for investigations in integrative and comparative biology. One
of the advantages for this route is that by using
cell-based systems, previously established methods
for engineering cells, genes, and proteins can be deployed among the entity’s encapsulated members.
This allows access to the wealth of advancements
made in these fields. Perhaps the most important
advantage is the protection of the artificial cell’s constituent members from immunorejection by the host
organism due to the protective barrier of the encapsulation. For example, encapsulated pancreatic islets
have been implanted into rats to treat diabetic conditions for a period of 2–3 weeks (Lim and Sun
1980). A protective membrane around the pancreatic
islet cells was formed by cross-linking alginate and
poly-lysine, which inhibited the host’s immunorejection response. Furthermore, other investigators
have widely used this approach to inhibit the
Fig. 3 Adding complexity to artificial cells. Compartmentation
(A) enables spatial segregation of different chemical reactions and
is a critical goal for adding to the complexity of the orthogonal
chemical reactions that an artificial cell may perform. Particularly
for mechanical studies, internal structure (B) can be engineered
(Zhang et al. 2007) and is important for eventually linking the
internal mechanics to external mechanics. The organization of
internal structure could enable these systems to function with
quite different responses, similar to the diverse behaviors observed in living cells with different cytoskeletal networks.
immunorejection of transplanted cells (Sun et al.
1996; Calafiore et al. 1999) and they have expanded
it to include other experimental models and cell
types (Chang 2005). The challenge posed by the
host organism’s inflammatory response to implanted
cells remains important along with issues of biocompatibility, stability, and reproducibility.
Artificial cell mechanics
Engineering mechanical structures and movement
into artificial cells will be especially important in
their application to comparative biomechanics studies. In a previous review, we defined several important properties required for biologically-inspired
artificial cell constructs (Zhang et al. 2008). These
functions included storage of cellular blueprints,
packaging of cellular products, synthesis of cellular
products, production of energy, synthesis of membrane compartments, and structural functions.
Of particular relevance for biomechanics is the structural integrity of the cell itself and its ability to locate
138
itself within its environment, as well as the cell’s ability to release internal molecular products in a controllable way. If these later-released products are
relevant to the host organism’s physiology, control
of its behavior could then be altered for experimental
biological studies. However, anchoring such artificial
cell controllers in their environment, along with enabling them to alter their movement and location
within their host organism, will also be important,
so artificial cell features that are inspired by cellular
biomechanics, such as an artificial cytoskeleton and
artificial motility, are relevant.
Work toward developing cells with artificial internal structure is well underway. Several studies have
described the encapsulation of actin networks within
the cellular liposomes (Miyata and Hotani 1992;
Honda et al. 1999; Zhang et al. 2007; Merkle et al.
2008). For example, Zhang et al. encapsulated
G-actin into giant, synthetic, and unilamellar vesicles
and then actin filaments were polymerized in these
liposomes. An example of a liposome with such an
internal structure is shown in Fig. 3. The structures
were visualized with epifluorescent and confocal microscopy and also probed with atomic force microscopy, revealing both the location of actin networks
within the liposome as well as an increase in mechanical strength. A similar study took this work
further by adding cross-linking proteins including
molecular motor proteins, such as fascin, a-actinin,
filamin, myosin-I isolated from brush border
(BBMI), and heavy meromyosin (HMM). When
these were encapsulated in liposomes, the homogeneity of the internal structure of the actin network
was radically altered, producing meshes similar to
those found in motile cells (Takiguchi et al. 2009).
As the engineering of internal structural members in
artificial cells advances, their integration with the cell
membrane and particularly with mechanical connections to the extracellular environment will be important. In living eukaryotic cells, this function is served
by the focal adhesion complex, which in addition to
being a signaling complex, serves to anchor the internal actin cytoskeleton to the external matrix, as
previously discussed. For engineering synthetic anchoring complexes in artificial cells, one promising
recent advance is the development of novel biomimetic stealth probes that anchor themselves within
lipid bilayers (Almquist and Melosh 2010). The functional part of these probes consists of an Au metal
layer functionalized with a hydrophobic band. The
layer then coats a nano-scale object of interest,
allowing the object to embed in a lipid bilayer.
The probes replicate the nanometer-scale hydrophilic–hydrophobic–hydrophilic
architecture
of
W. C. Ruder and P. R. LeDuc
transmembrane proteins and form a high-strength
interface with the membrane. If these probes can
be further functionalized to serve as nucleation
sites for actin polymerization intracellularly, and
ECM formation extracellularly, then artificial cells
may be more readily anchored in a tissue
environment.
Beyond these approaches for engineering artificial
intracellular structure, enabling cell motility—a cell’s
ability to move itself—will be important for artificial
cells that operate in a dynamic environment. Recent
work simulated colonies of biomimetic microcapsules designed to exploit chemical mechanisms that
communicate with each other. They could alter their
local environment and move with ant-like behavior
(Kolmakov et al. 2010). In the simulations, synthetic
objects self-organized in autonomously moving
structures. Signaling between microcapsules was
based on including some constructs that released agonists and others that released antagonists. The released particles could bind to the underlying
substrate, and created an adhesion gradient that propelled microcapsule movement. Through a combination of hydrodynamic forces and the released
particles, complex movements with the colonies of
simulated nonliving objects were observed. In other
studies involving synthetic approaches related to
movement, experimentalists harnessed fatty-acid
chemistry to construct oil droplets that moved directionally within chemical gradients and consumed
surfactant as a ‘‘fuel’’ (Hanczyc et al. 2007, Toyota
et al. 2009). By employing these methods, artificial
cells that could operate outside of tissue, in a liquid
suspension (such as in an organism’s circulation or
gut) may be realized.
Artificial cell intracellular transport
Enabling artificial cells with an ability to release their
contents in a controlled fashion will be important for
allowing them to regulate their environment. For example, if an artificial cell releases contents including
stimulants such as epinephrine, the behavior of a
host organism could be radically changed. We previously suggested one possibility for engineering release
of intracellular contents by first artificially pumping
protons into a compartment that contains a
pH-sensitive molecule capable of destroying lipid bilayers in response to acidity (Zhang et al. 2008).
Broadly, controlling the compartmentation of artificial cells will be critical in developing the behavior of
artificial cells to add molecular products to their environment. In the top-down context, this problem is
less of an issue because the constituents of the
139
Artificial cells in biomechanics
artificial cell entity are living cells themselves. They
already possess methods for extrusion and uptake of
environmental substances (e.g., exocytosis and endocytosis), and the behavior of these living systems can
be altered by addressing this extrusion on a molecular and genetic level. For example, researchers recently developed the Salmonella type III secretion
system to export spider silk monomers into the external environment (Widmaier et al. 2009). Artificial
cell constructs containing these engineered cells
could subsequently be engineered to release other
substances into their environment.
Artificial cells and synthetic biology
The potential combination of top-down-constructed
artificial cells with engineered constituent members
suggests a potential interplay between engineering of
artificial cells and a closely related field, synthetic
biology. In particular, one area of investigation in
synthetic biology, synthetic gene network engineering, aims to develop new cellular functions in
living cells, such as information processing. Highly
robust control structures like logic-gates, memory
modules, timers, and oscillators have been developed
(Khalil and Collins 2010). While the bottom-up approach to artificial cell engineering aims to create
these functions de novo, through the assembly of
chemical parts, a single cell-scale entity in the described top-down approach could harness these
already developed control structures by including
them in its constituents. For example, as shown in
Fig. 4, simple gene networks like bi-stable toggle
switches can be encoded into DNA (Gardner et al.
2000; Isaacs et al. 2004; Kobayashi et al. 2004; Khalil
and Collins 2010). By engineering the synthetic network into an artificial cell’s constituents, it would
gain this switching functionality. Furthermore, even
in the bottom-up approach, the design approach of
robust genetic control systems that have been engineered in synthetic biology can form a rubric for the
creation of similar systems formed by a combination
of chemical building blocks.
Fig. 4 Merging artificial cells with synthetic biological networks.
By utilizing the top-down approach to the assembly of artificial
cells, complex behaviors can be engineered into the artificial cell’s
constituents. Simple synthetic memory circuits, such as genetic
networks like bi-stable toggle switches (Gardner et al. 2000)
(upper section), can be assembled in DNA. For a toggle switch,
the DNA encodes two repressible promoters that each drives
the other’s repressor. As a result, only one repressor can be
expressed at any one time, forming a stable state. By encoding
this network into its constituents (lower left section), a
top-down-constructed artificial cell (lower right section) can be
engineered to possess simple memory.
potentially biocompatible artificial cells that result
in negligible damage to the integrity of the host’s
anatomy and physiology. While we are far from
the point at which implanted or ingested artificial
cells can prescribe the frequency at which a host organism should actuate its wings or fins, it is clear
that exogenous cells can cause changes in animals’
phenotypes. For example, a recent study linked the
gut flora of Drosophila melanogaster to its mating
preferences (Sharon et al. 2010). Clearly, commensal
microbes can alter the phenotype of eukaryotes. This
example provides inspiration for artificial cells eventually altering phenotype as well.
Concluding thoughts
We have begun to describe a framework for the development of biologically-inspired, small-scale devices that can act as cellular surrogates. The goal of
these approaches would be to alter the behavior of
multicellular host organisms. These synthetic surrogates, developed in the evolving field of artificial cell
engineering, represent a potential experimental approach for biomechanical studies in the future by
allowing organisms themselves to be probed with
Acknowledgments
The authors thank B. Flammang and M. Porter for
inviting them to be part of the Bioinspiration
symposium and providing them with helpful and
inspiring advice regarding comparative biomechanics. The authors are also grateful to the following
divisions of the Society for Integrative and
Comparative Biology for sponsoring the symposium:
the Division of Comparative Biomechanics, the
140
Division of Invertebrate Zoology, and the Division of
Vertebrate Morphology. The authors also thank
K. Dorgan and D. Evangelista for the many hours
of discussion regarding the potential role of artificial
cells, synthetic biology, and cellular biomechanics in
comparative biology.
Funding
The authors thank the Office of Naval Research and
the National Science Foundation for funding related
to this work.
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