Download Cell biology and cellular processes

Cell biology and cellular processes Systems biology for system engineers Part 3 Sofia Pe(ersson Informa9on Coding Dept. of Electrical Engineering Linköping University From genes to func9on Figure 8-3 Essential Cell Biology (© Garland Science 2010)
BIOLOGY OF ANIMAL CELLS Cell biology Molecule breakdown Cytoskeletal anchorage Protein sor:ng and modifica:on RNA transla:on Expresssion of lipids Energy produc:on Cell biology For the purpose of this seminar we will highlight the mitochondrion, the cell membrane and the cytoskeleton. Mitochondria Mitochondria are some9mes referred to as “power plants” as they generate adenosine triphosphate (ATP). They contain mitochondrial DNA (16 kilobases) that encodes genes for proteins and RNA (tRNA and rRNA). wikipedia.org
The cell membrane Lipid bilayer –  Fluid mosaic model –  Mobility in the plane, but not across the membrane –  Ac9ve transport required for charged, large molecules Transmembrane proteins –  Channels –  Cadherins and integrins (cell contact) –  Ligands and receptors (cell signaling) fsu.org
The cytoskeleton The cytoskeleton provides the cell with structural integrity, enables cell movement (migra9on) as well as molecular transport within the cell. The cytoskeleton is maintained by a balance of assembly and disassembly of its three types of protein filaments. Cellular movement and stress/contrac:on Mechanical strength Intracellular transport Microtubules The microtubules enable transport from the nucleus to the cytoplasm via motor proteins (kinesins and dyneins) and are crucial during cell division. Figure 17-17 Essential Cell Biology (© Garland Science 2010)
Cellular transport Essential Cell Biology (© Garland Science 2010)
Ac9n filament The ac7n filaments are thin and flexible, underlie the cell membrane, and are essen9al for cell morphology and migra9on. Figure 17-32 Essential Cell Biology (© Garland Science 2010)
Cell migra9on Essential Cell Biology (© Garland Science 2010)
CELL DIVISION Cell division Cell division does not only occur during development – cells replicate con9nuously. The rate varies between cell types and species and is affected by environmental changes. Table 18-1 Essential Cell Biology (© Garland Science 2010)
The cell cycle The different phases of the cell division program are specified in the cell cycle. The G0 phase is a res9ng phase and can be considered as an extension of the G1 phase, or as a quiescent state. Cell cycle checkpoints The cell passes a checkpoint before entering the next phase of the cell cycle. Figure 18-3 Essential Cell Biology (© Garland Science 2010)
DNA replica9on The helicase molecule unwinds the DNA-­‐helix into two strands. The two strands are then copied by DNA polymerase – one con9nuously (leading strand) and the other in segments (lagging strand). Essential Cell Biology (© Garland Science 2010)
Chromosome segrega9on The duplicated chromosomes are pulled apart during mitosis (nuclear and cytoplasmic separa9on) by the microtubules of the cytoskeleton. Figure 18-20 Essential Cell Biology (© Garland Science 2010)
Mitosis Cell division Essential Cell Biology (© Garland Science 2010)
CELL CONTACTS Cell contacts Most animal cells are contact-­‐dependent – a single cell in suspension will die. How cells form contacts with their surroundings depends on the extracellular environment. The extracellular environment In adult 9ssues and organs, cells are surrounded by extracellular matrix (ECM) proteins, inters99al fluid and other cells. The ECM contains 9ssue-­‐specific collagens and proteoglycans. Figure 20-10 Essential Cell Biology (© Garland Science 2010)
The extracellular environment During development, cells are surrounded by other cells and can, depending on species, come in contact with various substrates such as an egg shell. In later stages, ECM will be present as cells begin synthesis. wormclassroom.org
Cell–ECM contacts Cells adhere to the ECM via cell adhesion molecules (fibronec9n, vitronec9n, laminin etc.) that contain binding sites for both cell and ECM proteins. The transmembrane integrin molecules connect the cell adhesion molecules to the cytoskeleton. Figure 20-14 Essential Cell Biology (© Garland Science 2010)
Cell–cell contacts Cells adhere to other cells via transmembrane cadherin molecules, that are connected to the cytoskeleton via linker proteins. Figure 20-24 Essential Cell Biology (© Garland Science 2010)
Other cell-­‐cell junc9ons Though cadherin contacts are the most common (especially during development) there are several types of cell–cell junc9ons. Figure 20-22 Essential Cell Biology (© Garland Science 2010)
CELL SIGNALING Cell signaling There are several ways that cells communicate with each other Figure 20-22 Essential Cell Biology (© Garland Science 2010)
Receptors Receptors are proteins that bind specific molecules, ligands, according to a lock-­‐and-­‐key mechanism. They can be membrane-­‐bound or intracellular. Figure 16-8 Essential Cell Biology (© Garland Science 2010)
External signaling Signals origina9ng from the extracellular environment. Communica9ons range from long-­‐range influences to direct cell–cell interac9ons where both receptors and ligands are membrane-­‐bound. Figure 16-3 Essential Cell Biology (© Garland Science 2010)
Downstream effect of signal An external signaling event can either cause a transcrip9onal event OR cause an altered protein func9on without transcrip9on (cytoskeletal remodeling). Figure 16-7 Essential Cell Biology (© Garland Science 2010)
Biomechanical cues Not only biochemical signaling events affect cellular behavior – cells react to their surroundings in other ways. Inside-­‐out Cells contract and pull on their substrates, sensing their surroundings (other cells, the ECM etc) and prestressing the cell through the cytoskeleton. Flat morphology Stress fibers HI Less focal adhesions Substrate deforma:on SUBSTRATE STIFFNESS LOW Outside-­‐in Cells respond to external mechanical cues – compression, shear, tension and hydrosta9c pressure – by altering their morphology and/or gene ac9vity Some adult 9ssues depend on this type of signaling (bone, car9lage, blood vessels etc.) Shear Hydrosta:c Pressure Compression Shear Mechanotransduc9on Holle et al., Curr Op Biotechnology (2011)
Inside-­‐out The s9ffness of a substrate controls cell adhesion and morphology. Engler et al., Cell (2006)
Inside-­‐out The s9ffness of a substrate is sufficient to induce differen9a9on in adult stem cells (MSCs). Engler et al., Cell (2006)
Molecular strain gauges Molecular strain gauges Holle et al., Curr Op Biotechnology (2011)
Organizing the organism Each cell needs to be in the right place in the adult organism. During gastrula7on, cells are reposi9oned. For C. elegans, the E cells (making up the intes9ne) are transported into the central parts of the embryo. wormbook.org Organizing the organism Each cell needs to be in the right place in the adult organism. During gastrula7on, cells are reposi9oned. For C. elegans, the E cells (making up the intes9ne) are transported into the central parts of the embryo. This is achieved by cytoskeletal remodeling. wormbook.org Cell sor9ng Cells organize into subpopula9ons that will reform even if the cells are mixed. There are two hypothesis as to why: The differen7al adhesion hypothesis Cells sort with neighbors that express a similar cadherin pabern. Surface tension hypothesis Cells sort with neighbors that have similar mechanical proper9es. Lecuit et al., Nat Rev Mol Cell Biol (2007)
SYMMETRY-­‐BREAKING IN CELL LINEAGES Symmetry-­‐breaking in cell lineages Two main mechanisms for symmetry breaking ü External signaling ü Asymmetric cell division Through these events, various pathways are turned ON or OFF in the different cells (and subsequent lineages). Figure 8-19 Essential Cell Biology (© Garland Science 2010)
External signaling events Transcrip9onal ac9va9on through a conforma9onal change of an intracellular protein domain that moves into the cell nucleus. The Notch pathway is highly conserved and shared among species. wkipedia.org
Notch signaling in lineages In C. elegans, Notch signaling events establish differences between sibling cells throughout development. wormbook.org
Cell contact maps Notch signaling events require direct cell–cell contacts, but cell membrane posi9ons are difficult to determine. Hench et al., Dev Biol (2009)
Asymmetric divisions A cell polarizes its content (i.e. transcrip9on factors) prior to division, giving rise to two dis9nct daughters. The polariza9on is established by par99oning proteins and complex cor9cal flows (ac9n filaments). University of Washington (celldynamics.org) Asymmetric cell division wormbook.org Asymmetric division in cell lineages By separa9ng transcrip9on factors and/or their repressors through asymmetric division, different cell fate programs are ini9ated in embryonic cells. Hunter et al, Cell (1996)
From genes to func9on Capping, splicing and export Ac9va9on Transcrip9on ? What ini9ates and affects transcrip9on? ü Intracellular cell fate program ü Biochemical cues from the surrounding ü Mechanical cues from the surrounding Transport Transla9on Context Animal cells require mul9ple extracellular signals. The cell fate is determined by the intrinsic ability to respond to a signal (not all cells express the same receptors) and the sum of all signals. Figure 16-6 Essential Cell Biology (© Garland Science 2010)
The seminar series ü  ü  ü  1. Introduc:on (Robert Forchheimer, March 28) • The biological cell, the gene9c code, cell lineages. Terminology 2. From genes to func:ons (Sofia Pebersson, April 4) • Gene regula9on and transcrip9on 3. Cell biology (Sofia Pebersson, April 11) • Cellular processes 4. Synthe:c biology (invited speaker Erik Gullberg, Uppsala University, April 18) • IGEM-­‐2011/Team Uppsala 5. Models for cell and organism development (Jan-­‐Åke Larsson, April 25) • ODE-­‐ and PDE-­‐models. Boolean models 6. Case study (Invited speaker Thomas Bürglin, Karolinska Ins9tute, Huddinge, May 16) • C. elegans 7. Organism morphology and 3D-­‐modeling (Lena Klasén, May 23) • 3D-­‐modeling of cells and cell popula9ons