Cellular Self-Organization Flashcards
Define symmetry breaking
What properties does self-feedback product?
Robustness and bistability
What properties does feedback between entities produce?
Spatio-temporal patterning
What causes Turing patterns?
Reaction-diffusion of morphogens
What does the Gierer-Meinhardt model show?
Diffusible inhibitor
a is a short-range autocatalytic substance = activator
h is its long-range antagonist = inhibitor.
What is the limiting component of the diffusible inhibitor? ***
If activator inhibits the substrate, the substrate will be depleted
This occurs in cell polarity
How do patterns appear?
Patterns emerge from homogeneous states
Different patterns can appear after partial ablation
Define ultradian oscillation
Oscillations around 2-3hours
What occurs under ultradian oscillations?
Developmental processes
Cell proliferation
DNA damage responses
Immune responses
What is the relationship between p53 and mdm2?
Negative feedback loop
p53 causes transcription of mdm2
mdm2 inhibits p53 causing its degradation
What is p53?
Transcriptional factor that regulates genes for repair and cell death/sensescence
What is mdm2?
Ubiquitin-protein ligase
What type of oscillations does p53 show?
Sustained oscillations that are out of phase with mdm2
How can noise affect oscillations?
Noise can prevent oscillations from damping out
Noise-induced oscillations produce variable amplitudes, which increase with noise strength
What is a segmentation clock?***
The vertebrate segmentation clock is a molecular oscillator that regulates the periodicity of somite formation.
Three signalling pathways have been proposed to underlie the molecular mechanism of the oscillator, namely the Notch, Wnt and Fgf pathways.
What is the Hes gene and its alternate names?
Hairy and Enhancer of Split-1 = in mammalian systems (Her in zebrafish)
Hes genes are downstream targets of the Notch pathway that encode transcriptional repressors.
These repressors are likely to establish negative feedback loops by repressing their own transcription,
What is Hes7 and its roles?
Repressive transcription factor that targets its own promoter
Essential for somitogenesis and neurogenesis
What is Cdc42?
GTPase regulator of cell polarity and morphogenesis in eukaryotes
GTPases are activated by GEF, allowing GDP to dissociate and GTP to bind
What is the role of Cdc42?
GTPase causing activation of WASP and resulting in actin polymerization
Allowing, in this case, yeast to chagne orientation
What is FRAP?
Fluorescence recovery after photobleaching
What does FRAP show in terms of Cdc42?
FRAP gives a measure of kinetics of protein diffusion and binding
Showing Cdc42 has a fast turnover at memrbane site
What doe LatA do?
Blocks actin filament assembly
What are Bem-1 and F-acting requried for?
Polarity
Bem-1 = GEF
F-actin = part of cytoskeleton
What happens with overexpression of Bem1-GEF or Cdc42 GEF?
Leads to multiple dynamic clusters in yeast = too many budding sites per cell
What does parallel positive feedback by Bem1 and F-acin cause in Cdc42?
Both would lead to overexpression of Cdc42
What is the outcome of positive feedback on cell polarity?
Leads to robust generation of cell polarity, which is an example of symmetry breaking
What does E.coli allow us to study?
Useful model system for PROTEIN OSCILLATION
How is a standing wave produced?
When two waves are travelling towards each other in opposing direction
They produce a standing wave, which only moves up and down not left to right
What proteins show oscillations in E.coli?
Min proteins
What is the role of FtsZ ring?
What is the role of MinC?
Inhibits formation of FtsZ ring
What is the role of MinD?
ATPase that when bound to ATP attaches to membrane
MinC binds MinD forming MinCD complex, which oscillates from pole to pole inhibitng FtsZ ring formation at poles
What is the role of MinE?
MinE regulates activity of MinD = promotes disassembly of MinCD complex at cell poles and centre
Describe the feedback loop between minD and minE
MinD is autoactivated
MinD activates MinE
MinE has a delayed inhibition of MinD
What is chemotaxis?
This is the movement of an organism or cell toward or away from a soluble chemical stimulus
What is haptotaxis?
The directed movement of cells in response to a gradient of adhesion molecules or other surface-bound cues = immobilized chemicals
What is durotaxis?
Cells move in response to differences in the mechanical stiffness or rigidity of their substrate.
Softer materials might be found in areas undergoing tissue repair, while stiffer materials could be associated with more mature tissue.
Cells form attachments to their substrates through structures called focal adhesions. On stiffer surfaces, cells can form stronger focal adhesions, leading to increased traction forces that enhance their ability to move.
What are the regions of cytoskeleton polarization?
Front = actin polymerization
Back = myosin contraction
What are filopodia and how are htey formed?
Filopodia are slender, finger-like projections that extend from the leading edge of a migrating cell.
They are formed by the polymerization of actin filaments, activated by Cdc42
What are lamellipodium?
Lamellipodia are broad, sheet-like extensions formed at the leading edge of migrating cells. They arise from the polymerization of a branched network of actin filaments, largely regulated by the Arp2/3 complex, which is activated by Rac.
What are stress fibres?
Stress fibres are contractile bundles of actin filaments, often composed of a thicker array of actin filaments along with myosin motor proteins
Facilitated by Rho
Which signalling pathway do Hem-1 and WAVE/SCAR act in?
Act downstream of Rac1
Specifically involved in actin dynamics and the formation of lamellipodia
What are focal adhesions and their role?
Focal adhesions are complex structures formed at the points where the cell membrane adheres to the extracellular matrix. They develop as a result of interactions between integrin receptors on the cell surface and the extracellular matrix components.
Facilitated by Rho
What is Hem-1?
Hem-1 is a key component of the WAVE complex
Upon activation by Rac1, Hem-1 helps stabilize and promote the assembly of the WAVE complex at the leading edge of the cell.
What is the role of WAVE/SCAR?
When Rac1 is activated it binds WAVE/SCAR.
Hem-1 facilitates the interaction between Rac1 and the WAVE complex.
WAVE/SCAR comlex are activators of Arp2/3 = leading to enhanced activation of the Arp2/3 complex
How is actin polarization explained by negative feedback loops?
Nucleation-promoting factor and negative feedback from actin filaments generates spontaneous polymerization waves
What happens to Hem-1 waves at mechnaical barriers?
Waves are extinguished
Tension in the cytoskeleton changes, which can lead to Rho activation and Rac inhibition
