Periodic Reporting for period 4 - MicMactin (Dissecting active matter: Microscopic origins of macroscopic actomyosin activity)
Reporting period: 2020-12-01 to 2022-05-31
We bridge this gap through multiscale models of the emergence of active material properties in the experimentally well-characterized actin cytoskeleton. We thus investigate unexplored, strongly interacting nonequilibrium regimes. We develop a complete framework for cytoskeletal activity by separately studying all three fundamental processes driving it out of equilibrium: actin filament assembly and disassembly, force exertion by branched actin networks, and the action of molecular motors. We then recombine these approaches into a unified understanding of complex cell motility processes.
To tackle the cytoskeleton’s disordered geometry and many-body interactions, we design new nonequilibrium self-consistent methods in statistical mechanics and elasticity theory. Our findings are being validated through simulations and close experimental collaborations.
Our work breaks new ground in both biology and physics. In the context of biology, it establishes a new framework to understand how the cell controls its architecture and mechanics through biochemical regulation. On the physics side, it sets up new paradigms for the emergence of original out-of-equilibrium collective behaviors in an experimentally well-characterized system, addressing the foundations of existing macroscopic “active matter” approaches.
Task 2 – growing branched networks: We have shed light on force generation by growing actin filaments in the presence of actin growth regulators in collaboration with experimentalists (eLife publication). We have set up a simulation framework and a theoretical model that describe branched actin network elasticity as caused by filament entanglements and agree with experiments (Science Advances and Nature Physics publications, manuscript in preparation). We have advanced our fundamental understanding of the viscoelastic behaviour of networks in collaboration with experimentalists (Macromolecules publication).
Task 3 – force generation and transmission: We have shown that contractile stresses are both amplified and rectified by fiber networks (publication in PNAS), and are currently establishing these principles as universal in nonlinear elastic networks (publications in Soft Matter). In collaboration with experimentalists, we have established a new inference method allowing the validation of our results in experiments, which will allow monitoring the time evolution of contractility among others (second publication in PNAS). Finally, we have elucidated the fundamentals of force generation in disordered actin networks in the absence of filament nonlinear response (eLife publication).
Task 4 – putting it all together: We have uncovered new principles underlying the collective stability of active systems in several different contexts, which provides fundamental insights required to study the collective dynamics of the cell (PNAS, Nat. Commun. and Phys. Rev. Lett.).
Task 2 – growing branched networks: We have elucidated force-generation mechanism in growing actin filaments in the presence of formin. We have collected results on the entanglement topology of growing actin trees and are putting together simulations on their linear and nonlinear elasticity. We are now moving forward to use these results to obtain a fuller understanding of the elasticity of branched actin networks.
Task 3 – force generation and transmission: We have demonstrated new mechanisms for contractile force generation in actin networks in the absence of preexisting filament and motor organization, shedding light on disordered, contractile structures in vivo. We are now working to establish a systematic comparison between these mechanisms and generate specific, testable predictions for active force generation in cells.
Task 4 – putting it all together: We have demonstrated unknown stabilization mechanisms in active nematic, polar and chiral active systems. We have started collaborating with experimentalists and will integrate our results on the first three tasks to describe the response of the morphology, mechanics and dynamics of whole cells to osmotic shocks.