How Actin Polymerization Provides Force to Move Cells and Change Their Shape

Lecturer:
Prof. Anders Carlsson (Washington University in St. Louis)

Dates:
October 17 and 24, 2016

Time:
Mondays: 10:15 - 11:45

Place:
EW 202 (TU Berlin, EW-building)

The functions of biological cells are driven by complex networks of proteins and other key molecules. Most theoretical analysis of such networks has been based on a purely chemical picture, but it is becoming increasingly clear that mechanical force is a key input into the network behavior. The intracellular protein actin is one of the key force-producing agents in the cell. It can polymerize into semiflexible filaments, which can propel a cell forward and change its shape. The lectures will present key experimental and biological background, demonstrate using a variety of theoretical tools how actin can generate pushing forces, describe how force generation by actin is regulated from upstream, and finally show how actin-based force generation drives endocytosis.

I) Observational background

   A) Cell migration
   B) Propulsion of pathogens
   C) Cell shape changes
   D) Measurements of actin-based forces

II) Theory of pushing force generation by actin polymerization

   A) Molecular properties of actin
   B) Equilibrium and nonequilibrium polymerization
   C) Rigorous properties of equilibrium actin force generation
   D) Brownian-Ratchet model
   E) Effects of filament/membrane flexibility
   F) Multifilament effects
   G) Nonequilibrium force generation

III) Control of actin-based force generation

   A) Actin filament nucleation
   B) Feedback of actin onto its nucleators
   C) Actin waves
   D) Actin pulses in endocytosis

IV) Theory of pulling force generation by actin polymerization

   A) Implications of force balance
   B) How actin polymerization drives endocytosis

Recommended literature

1. J. Howard, Mechanics of Motor Proteins and the Cytoskeleton, Chapters 1-11, Sinauer (2001).
2. A. Mogilner, Mathematics of cell motility: have we got its number?, J. Math. Biol. 58, 105-134 (2009).
3. A. E. Carlsson and D. Sept, Mathematical modeling of cell migration, Methods in cell biology 84, 911-937 (2008).