S4E4

Abstract

Cell migration on 2D substrates is typically characterized by lamellipodia at the leading edge, mature focal adhesions, and spread morphologies. These observations result from studies of cell migration on rigid or stiff elastic substrates, as most cells do not migrate on compliant, elastic substrates. However, many biological tissues are compliant, with an initial elastic modulus on the order of ~1 kPa, and are viscoelastic, exhibiting stress relaxation over time in response to deformation.

Here, we systematically investigate the impact of substrate stress relaxation on cell migration on compliant substrates with tunable substrate stress relaxation half times (~100 seconds to ~2,000 seconds). We find that cells did not migrate on slow-relaxing substrates but migrated robustly on fast-relaxing substrates. Strikingly, migrating cells on compliant viscoelastic substrates were not spread, did not extend lamellipodial protrusions, but were instead rounded, with filopodia protrusions extending at the leading edge, and exhibited nascent adhesions. Motor-clutch-based computational modeling predicted the observed impact of stress relaxation on cell migration. Taken together, our findings establish substrate stress relaxation as a key requirement for robust cell migration on compliant substrates and uncover a previously undescribed mode of cell migration marked by round morphologies, filopodia protrusions, and weak adhesions.

Introduction of speaker

Dr. Kolade Adebowale is currently a postdoctoral fellow in bioengineering at Harvard University / Wyss Institute. He received his Ph.D. in chemical engineering from Stanford University. His research interests lie at the interface of material science and biology. At Stanford, he demonstrated that biomaterial viscoelasticity is a key regulator of cancer cell migration. At Harvard, he is investigating how adoptive immune cell therapies traffic through extracellular matrices and solid tumors. Outside of the lab he enjoys hanging out with friends, photography, traveling, and exploring cities. He is looking to continue his independent research in a tenure-track position.

Abstract

We present an approach to solving problems in micromechanics that is amenable to massively parallel calculations through the use of graphical processing units and other accelerators. We demonstrate the approach by studying liquid crystal elastomers (LCEs), an emerging class of responsive materials, that are obtained by incorporating nematic mesogens into the underlying polymer chains of the elastomer. Various problems of micromechanics, including those of LCEs, lead to nonlinear differential equations that are typically second order in space and first order in time. This combination of nonlinearity and nonlocality makes such problems difficult to solve in parallel. However, this combination is a result of collapsing nonlocal, but linear and universal physical laws (kinematic compatibility, balance laws), and nonlinear but local constitutive relations. We propose an operator-splitting scheme inspired by this structure. The governing equations are formulated as (incremental) variational problems, the differential constraints like compatibility are introduced using an augmented Lagrangian, and the resulting incremental variational principle is solved by the alternating direction method of multipliers. The resulting algorithm has a natural connection to physical principles, and also enables massively parallel implementation on structured grids. We apply the method to study polydomain LCEs where disorder disrupts natural nematic order. Our simulations reveal a new and unexpected liquid-like behavior in membranes, as well as the mechanism for this exotic behavior.

Introduction of speaker

Dr. Hao Zhou obtained his Ph.D. degree from the Department of Mechanical Engineering at the California Institute of Technology, working with Prof. Kaushik Bhattacharya. He received his bachelor's degree from Peking University in 2016. His research focuses on the development of computational micromechanics algorithms and the behavior of soft materials.