Professor Yi Wang
Physics
Chinese University of Hong Kong - Physics Department
Hong Kong

Thursday, September 30, 2021
11:00 am (CT)
Zoom webinar recording

Abstract

Cell-adaptable hydrogels crosslinked by reversible bonds provide an ideal environment mimicking the highly dynamic extracellular matrix. Unlike cell-mediated matrix degradation, the dynamic nature of these adaptable hydrogels relies on intrinsically reversible crosslinks. Here, we combine microsecond molecular dynamics simulations, adaptive biasing force as well as kinetic Monte Carlo calculations to investigate the role of binding kinetics in regulating cell spreading within hydrogels formed by hyaluronic acid grafted with either adamantane (HA-ADA) or cholic acid (HA-CA) via cyclodextrin (CD)–ADA or CD–CA host–guest complexation. With the host-guest crosslinks forming the 'gates' blocking cell spreading, we show that the probability of a ‘fast enough’ gate opening event, i.e., the gate opens within the typical actin polymerization timescale, increases with an increasing percentage of the fast CD-ADA crosslinks in the hydrogels. Along with our collaborators' experiments, these computer modelling results pinpoint the critical role of binding kinetics in regulating cell spreading --- given similar equilibrium binding constants, hydrogels containing dynamic crosslinks with a large dissociation constant enable cell force- induced network reorganization, which results in rapid stellate spreading, assembly, mechanosensing, and differentiation of encapsulated stem cells when compared to similar hydrogels containing dynamic crosslinks with a low dissociation constant.

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