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March 13 Colloquium

Kwonmoo Lee, Harvard Medical School

Integrating Protein Dynamics and Cell Mechanics: Mechanosensitivity of Dynamic Actin Remodeling During Cell Migration

Migrating cells are mechanochemical machines where biochemistry and mechanics integrate to control cellular motion. The polymerization of the filamentous protein called actin provides force generation for membrane protrusion, an initial step of cell migration. In turn, mechanical force sensed by cells leads to dynamic responses of the intracellular biochemical pathways. The dissection of systems with such mechanochemical pathways has remained a fundamental challenge in biological investigation.

To unravel the complex nature of interplay between biochemistry and mechanics in space and time, we developed a novel statistical approach based on local image sampling and registration to directly visualize the dynamics of molecular/cellular events at the subcellular level. This method revealed distinct dynamics of molecular factors and traction force involved in cell protrusion, allowing us to establish in situ their differential functions. This quantitative framework also allowed us to exploit natural heterogeneity of cell protrusion to extract statistical relationships between different molecular/cellular events. Using this method we suggest that linear actin filaments along with adhesion formation initiate new protrusions. Then, the linear filaments undergo a structural transition to branched networks, mediated by exponential actin polymerization. Furthermore, we showed that increasing membrane tension during protrusion promotes this structural tension which leads to stronger force generation to support edge advancement against the membrane tension. This suggests that migrating cells can reorganize their biochemical machinery in response to mechanical cues in a highly dynamic manner at a time scale of 10 seconds. It also highlights that mechanical processes are tightly integrated with biochemical pathways and modulate protein dynamics, thereby playing critical roles in cell physiology.

REFRESHMENTS:  3:40 p.m. in the Willamette Atrium COLLOQUIUM:   4:00 p.m. in Willamette 100