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

Protein sor:ng and modifica:on Energy produc:on

Expresssion of lipids

RNA transla:on Molecule breakdown

Cytoskeletal anchorage

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.

Mechanical strength

Intracellular transport Cellular movement and stress/contrac:on

Microtubules


The microtubules enable transport from the nucleus to the cytoplasm via motor proteins (kinesins and dyneins) and are crucial during cell division.

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.

Cell migra9on


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.

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).


Chromosome segrega9on


The duplicated chromosomes are pulled apart during mitosis (nuclear and cytoplasmic separa9on) by the microtubules of the cytoskeleton.

Mitosis

Cell division


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.

The extracellular environment

wormclassroom.org

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.

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.

Cell–cell contacts


Cells adhere to other cells via transmembrane cadherin molecules, that are connected to the cytoskeleton via linker proteins.

Other cell-‐cell junc9ons


Though cadherin contacts are the most common (especially during development) there are several types of cell–cell junc9ons.

CELL SIGNALING

Cell signaling


There are several ways that cells communicate with each other

Receptors


Receptors are proteins that bind specific molecules, ligands, according to a lock-‐and-‐key mechanism. They can be membrane-‐bound or intracellular.

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.

Downstream effect of signal


An external signaling event can either cause a transcrip9onal event OR cause an altered protein func9on without transcrip9on (cytoskeletal remodeling).

Biomechanical cues Not only biochemical signaling events affect cellular behavior – cells react to their surroundings in other ways.

Inside-‐out

HI SUBSTRATE STIFFNESS LOW

Flat morphology Stress fibers

Less focal adhesions Substrate deforma:on

Cells contract and pull on their substrates, sensing their surroundings (other cells, the ECM etc) and prestressing the cell through the cytoskeleton.

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.)

Compression

Shear

Hydrosta:c Pressure

Shear

Mechanotransduc9on

Holle et al., Curr Op Biotechnology (2011)

Inside-‐out

Engler et al., Cell (2006)

The s9ffness of a substrate controls cell adhesion and morphology.

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

Lecuit et al., Nat Rev Mol Cell Biol (2007)

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.

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).

External signaling events

wkipedia.org

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.

Notch signaling in lineages

wormbook.org

In C. elegans, Notch signaling events establish differences between sibling cells throughout development.

Cell contact maps

Hench et al., Dev Biol (2009)

Notch signaling events require direct cell–cell contacts, but cell membrane posi9ons are difficult to determine.

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

Hunter et al, Cell (1996)

By separa9ng transcrip9on factors and/or their repressors through asymmetric division, different cell fate programs are ini9ated in embryonic cells.

From genes to func9on

Transcrip9on Transla9on

Ac9va9on Capping, splicing and export Transport

What ini9ates and affects transcrip9on? ü Intracellular cell fate program ü Biochemical cues from the surrounding ü Mechanical cues from the surrounding

?

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.

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

ü  ü  ü 

The seminar series

Cell biology and cellular processes

Documents

Transcript of Cell biology and cellular processes