Cell mechanics, control and energetics of actomyosin cortex
The actomyosin cortex, consisting of filamentous actin, myosin molecular motors and various cross-linking proteins, is a key cellular machinery that regulates cell mechanics and cell shape. To understand how this multi-component system gives rise to emergent mechanical properties, we used a reconstituted system to study how cross-linker protein concentration modulates the structure and dynamics of actomyosin cortex. We discover that as the amount of cross-linking is tuned, the system transitions from a free-flowing state with maximal susceptibility to a contractile state, suggesting that cross-linker concentration could be used to induce major structural reorganization in the actomyosin cortex and dynamically regulate cell mechanics.
To further study how upstream Rho signaling control actomyosin contractility to regulate cell shape, we develop optogenetic Rho constructs in sea star oocytes. Using spatiotemporally-patterned light stimuli as a control input, we create chemomechanical cortical excitations that are decoupled from meiotic cues and drive diverse shape deformations ranging from local pinching to surface contraction waves and cell lysis. Further, by constructing a quantitative model that consider mechanical and chemical dynamics, we are able to predict and program transitions in shape dynamics. Results from this optogenetic study pave the way towards real-time control over dynamical shape changes in living organisms.
Other than self-organization and control, another important aspect of understanding cell mechanical machinery is energetics. Cellular structures constantly consume and dissipate energy on a variety of spatiotemporal scales in order to function. Their inherent multi-scale nature makes it challenging to unravel the mechanisms underlying the observed nonequilibrium activity. By analyzing probe particles embedded in the starfish oocyte cortex and using a multi-scale irreversibility metric, we extract model-independent estimates of the time-scales of energy dissipation. We further demonstrate that the irreversibility measure maintains a monotonic relationship with the underlying biological nonequilibrium activity. More generally, this irreversibility metric can be used to identify activity time scales in various biological systems. Altogether, these projects elucidate the mechanochemical principles underlying the cell contractile machinery driven by actomyosin cortex.
Tan TH*, Malik-Garbi M*, Abu-Shah E*, Li J, Sharma A, MacKintosh FC, Keren K, Schmidt CF and Fakhri N, (2018) “Self-organized stress patterns drive state transitions in actin cortices.” Science Advances, 4(6), p.eaar2847. See also: F1000 article recommendation
Tan TH*, Watson GA*, Chao YC*, Gingrich TR, Horowitz JM, and Fakhri N “Scale-dependent irreversibility in living matter.” arXiv 2022.