Poster

Modeling cell contact guidance on alternating stiffness substrates without topographic variations

mathis grelier¹, carlos ureña martin², mark schvartzman², ana-sunčana smith^1,3

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Understanding cellular responses to substrate stiffness is fundamental for studying cell spreading and migration [1,2,3]. Our study investigates the contact guidance of HeLa cells by conducting experiments on substrates with alternating stripes of distinct stiffness, without topographic variations. We introduce a stochastic model based on a Boltzmann distribution to describe cell spreading, considering various energy contributions [4] that affect cell movement across stiffness boundaries. Our findings show that cells align more along softer stripes as their width increases due to the higher energy required for cells to traverse softer substrates. This model successfully captures the probability distribution of cell shapes and alignments observed in experiments, providing a quantitative framework for predicting cell migration biomechanics across substrates of varying stiffness.

To compare these results with other experiments—such as those involving different substrate stiffness values or the application of drugs like blebbistatin or cytochalasin—we applied a Globalized Bounded Nelder-Mead optimization [5,6]. This approach enhances the identification of physical quantities, such as stiffness and cell contractility, that best align the model with experimental data. It allows us to efficiently explore a broad range of these quantities and determine the effects of drugs on them. Notably, our results suggest that cell behavior is relatively insensitive to variations in the stiffness of softer regions but highly responsive to changes in the stiffness of rigid regions. These insights enhance our understanding of the mechanical cues driving cellular behavior on patterned substrates and demonstrate the robustness of our model in predicting cell dynamics.