Download Biological background of cell-ECM interactions

Modelling the Interactions of
Cells with the Environment
Luigi Preziosi
Dept Mathematical Sciences
Politecnico di Torino
[email protected]
Http://calvino.polito.it/~preziosi
Index
How do cells interact mechanically with the environment?
Why is it important?
What has been done from the modeling point of view?
Index
How do cells interact mechanically with the environment?
Why is it important?
What has been done from the modeling point of view?
Biological background
The cytoskeleton is an intricate network of protein filaments
that extends throughout the cytoplasm.
Biological background
The cytoskeleton is an intricate network of protein filaments
that extends throughout the cytoplasm.
Functions of the cytoskeleton
• Structural support for the
cytoplasm
• Causes changes in cell shape
• Drives cell division
• Causes cell movements
• Causes muscle contraction
• Controls location of
organelles
• Provides transport between
organelles
The actin cytoskeleton
www.youtube.com/watch?v=saYK4Xseg2g
• Keratocyte
• Keratocyte fragment
A. Verkhovsky
T
Actin polymerisation
(Pantaloni and Carlier, 2002)
Actin filaments
 Actin filaments are concentrated
beneath the plasma membrane (cell
cortex) and give the cell mechanical
strength.
 Assembly of actin filaments can
determine cell shape and cause cell
movement.
 Association of actin filaments with
myosin can form contractile structures.
www.sci.sdsu.edu/movies/actin_myosin_gif.html
Motor proteins
• Motor proteins bind to actin
filaments and microtubules
and move by cycles of
conformational changes
using energy from ATP.
• One end of the protein can
bind to specific cellular
components.
myosin
Original at: www.youtube.com/watch?v=vJ9ffKeUCvE&hl=it
Cell crawling
• Motion of a melanoma cell
• Motion of a fibroblast
Original at: cellix.imba.oeaw.ac.at/fileadmin/conferences/Videotour_CellMotility/fig3.mov
(Burridge & Chrzanowska-Wodnick)
(Burridge et al. Trends Cell Biol. 7, 342-347, 1997)
Cell crawling
Cell crawling
Focal contacts
• Focal contacts and microtubulin
• Animation focal contact and cytoskeleton
• Making a focal contact
(cellix.imba.oeaw.ac.at/fileadmin/conferences/Videotour_CellMotility/fig40.mov
fig26.mov fig15.mov)
Extra-cellular matrix
Extra-cellular matrix
(P. Friedl)
Index
How do cells interact mechanically with the environment?
Why is it important?
What has been done from the modeling point of view?
Mechanosensing & mechanotransduction
Mechanosensing = How cells sense mechanical forces
Mechano-transduction = How cells respond to mechanical signals,
either directly or via the activation of signalling pathways
Macroscopic
force
Macroscopic
force
Cell traction
Mechanosensing & mechanotransduction
Mechanosensing = How cell celse mechanical forces
Mechano-transduction = How cell respond to mechanical signals,
either directly or via the activation of pathways
Sun, Chen, Fu, Forcing stem cells to behave: A biophysical
perspective of the cellular microenvironment
Ann. Rev. Biophys. 41, 519-542 (2012)
Guilak, … & Chen, Control of stem cells
by physical interaction with the ECM,
Cell Stem Cell 5, 17-26 (2009)
Diseases of mechanotransduction
Abnormal conversion of mechanical stress
into intracellular gradients of electrical activity
Stretch activated signalling cascades
due to stents and grafts
Abnormal ECM accumulation
Stretching of mesangial cells through ECM
and integrins due to glomerular hypertension
Vasculature feels and
adapt to shear and pressure
Dementhia
Ingber, Mechanobiology and diseases of mechanotransduction
Annals Medicine 35, 1-14 (2009)
Diseases of mechanotransduction
Loss of contact inhibition
Matrix Metallo Proteinases
Excessive production of ECM
Insufficient mechanosensing
Enhanced ECM breakdown
Excessive ECM
Cell hypercontractility
Tumour-stroma interaction
Relations between ECM stiffness and cell tensile stress influences
Proliferation
Kass, Erler, Dembo & Weaver, Mammary epithelial cell
Apoptosis
Influence of ECM composition and organization during
Migration
development and tumorigenesis
Int J Biochem Cell Biol 39, 1987-94 (2007)
Tumour-stroma interaction
Butcher, Alliston & Weaver,
A tense situation: forcing tumour progression
Nat Rev Cancer 9, 108-122 (2009)
Tissue engineering: Controlling stem cell fate
Control of stem cell fate:
Genetic and molecular mediators
(growth factors, transcription factors, …)
ECM interaction
ECM elasticity
ECM morphology
ECM mediated stress
Jones & Wagers, No place like home:
Anatomy and function of the stem cell niche
Nature Rev 9, 11-22 (2008)
Mechano-reciprocity
It mantains tensional homeostasis in the tissue
Is necessary for development and tissue-specific differentiation
Its loss promotes disease progression, including liver fibrosis, atherosclerosis and cancer
Butcher, Alliston, Weaver,
A tense situation: forcing tumour progression
Nat Rev Cancer 9, 108-122 (2009)
Mechano-reciprocity
Mechano-reciprocity
Mechano-reciprocity
Franzè, The mechanical control of nervous system development
Development 140, 3069-3077 (2013)
Building stem cell niches
Jones & Wagers, No place like home: Anatomy and function of the stem cell niche, Nature Rev 9, 11-22 (2008)
Lindvall, Kokaia, Stem cells in human neurodegenerative disorders: Time for clinical translation?
J. Clinical Inv 120, 29-40 (2010)
Progress stem cells for the treatment of neurological disorders, Nature 441 1094-1096 (2006)
Lindvall, Kokaia, Stem cells in human neurodegenerative disorders: Time for clinical translation?
J. Clinical Inv 120, 29-40 (2010)
Progress stem cells for the treatment of neurological disorders, Nature 441 1094-1096 (2006)
Lindvall, Kokaia, Stem cells in human neurodegenerative disorders: Time for clinical translation?
J. Clinical Inv 120, 29-40 (2010)
Progress stem cells for the treatment of neurological disorders, Nature 441 1094-1096 (2006)
T
Lindvall, Kokaia, Stem cells in human neurodegenerative disorders: Time for clinical translation?
J. Clinical Inv 120, 29-40 (2010)
Progress stem cells for the treatment of neurological disorders, Nature 441 1094-1096 (2006)
Interaction with ECM micropatterns
Cell-ECM contact are regulators of cell function
Guilak, … & Chen, Control of stem cell fate by physical interaction with the ECM
Cell Stem Cell 5, 17-26 (2009)
Interaction with ECM micropatterns
Interaction with ECM micropatterns
Théry, ... & Julicher
Experimental and theoretical study
of mitotic spindle orientation
Nature 447, 493-497 (2007)
Building a proper artificial ECM
Building a proper artificial ECM
Stevens & George, “Exploring and engineering the cell surface interface”, Science 310, 1135-1138 (2005)
Tissue engineering: building the stem cell niche
Tactile sensors
Flow sensors