Theoretical Soft Matter and Biophysics Group

Our research focuses on the non-equilibrium mechanics and collective behavior in biological systems and soft matter. One central theme is the investigation of the nature of solid-fluid transitions in amorphous systems, ranging from biological tissues and cancer tumors to colloids and granular materials. We use theoretical and numerical tools from biophysics, non-equilibrium statistical physics, condensed matter physics, and glassy physics to model and understand the complexity, patterns, and mechanical response that arise from the collective organizations of individual constituents (e.g., biological cells, grains, colloids).

Shear-driven solidification and nonlinear elasticity in epithelial tissues

Biological processes, from morphogenesis to tumor invasion, spontaneously generate shear stresses inside living tissue. The mechanisms that govern the transmission of mechanical forces in epithelia and the collective response of the tissue to bulk shear deformations remain, however, poorly understood. Using a minimal cell- based computational model, we investigate the constitutive relation of confluent tissues under simple shear deformation. We show that an initially undeformed fluid-like tissue acquires finite rigidity above a critical applied strain. This is akin to the shear-driven rigidity observed in other soft matter systems. Interestingly, shear-driven rigidity can be understood by a critical scaling analysis in the vicinity of the second order critical point that governs the liquid-solid transition of the undeformed system. We further show that a solid-like tissue responds linearly only to small strains and but then switches to a nonlinear response at larger stains, with substantial stiffening. Finally, we propose a mean-field formulation for cells under shear that offers a simple physical explanation of shear-driven rigidity and nonlinear response in a tissue.

Related Publication(s):

J. Huang et al “Stress-driven rigidity and non-linear elasticity in epithelial tissues.” (2021). Preprint:

Glassy Behavior, Intermittency, and Cell Streaming in Epithelial Tissues

Embryonic development, tissue repair, and cancer progression all rely on neighboring cells rearranging themselves in biological tissue. One basic unit of such movement of cells in close-packed tissues is the T1 transition, where two cells swap positions. Because of the time required to remodel complex structures at junctions between cells, T1 transition cannot occur instantaneously. How this biological constraint affects collective behaviors among cells inside tissues is not known. Using theoretical modeling and simulations, we demonstrate that cell-level control of the time it takes to complete a T1 transition has unique consequences that change the ways cells mechanically interact, collectively organize, and migrate.

Related Publication(s):

Configurational fingerprints of multicellular living systems

Cells cooperate as groups to achieve structure and function at the tissue level, during which specific material characteristics emerge. Analogous to phase transitions in classical physics, transformations in the material characteristics of multicellular assemblies are essential for a variety of vital processes including morphogenesis, wound healing, and cancer. In this work, we develop configurational fingerprints of particulate and multicellular assemblies and extract volumetric and shear order parameters based on this fingerprint to quantify the system disorder. Theoretically, these two parameters form a complete and unique pair of signatures for the structural disorder of a multicellular system. The evolution of these two order parameters offers a robust and experimentally accessible way to map the phase transitions in expanding cell monolayers and during embryogenesis and invasion of epithelial spheroids.

Related Publication(s):

Unjamming transition vs. the Epithelial-to-Mesenchymal transition in epithelial tissues

The epithelial-to-mesenchymal transition (EMT) and the unjamming transition (UJT) each comprises a gateway to cellular migration, plasticity and remodeling, but the extent to which these core programs are distinct, overlapping, or identical has remained undefined. Here, we triggered partial EMT (pEMT) or UJT in differentiated primary human bronchial epithelial cells. After triggering UJT, cell-cell junctions, apico-basal polarity, and barrier function remain intact, cells elongate and align into cooperative migratory packs, and mesenchymal markers of EMT remain unapparent. After triggering pEMT these and other metrics of UJT versus pEMT diverge. A computational model attributes effects of pEMT mainly to diminished junctional tension but attributes those of UJT mainly to augmented cellular propulsion. Through the actions of UJT and pEMT working independently, sequentially, or interactively, those tissues that are subject to development, injury, or disease become endowed with rich mechanisms for cellular migration, plasticity, self-repair, and regeneration.

Related Publication(s):

Effect of phenotypic heterogeneity in epithelial layers

Heterogeneity amongst cells in a tumor has been recognized as one of the hallmarks of cancer. This so-called intratumor heterogeneity is thought to facilitate metastasis by allowing a cellular community the flexibility and efficiency to adapt to new environments. It is also largely responsible for therapeutic resistance. Cellular differences within a tumor result from an interplay of both genetic and extrinsic influences. Whereas fitness or genotypic heterogeneity has been studied extensively, the role of mechanical heterogeneity in a tumor or cellular collective is still not well understood.

Related Publication(s):

Understanding the Origin of Mechanical Rigidity in Biological Tissues

Every organ in the human body is lined with epithelial cells. The cells in these tissues are normally sedentary or solid-like but become migratory or fluid-like during embryonic development, tissue repair, and cancer invasion. Researchers do not understand this striking transition from stationary to active behaviors, which could help shed light on various aspects of biology, medicine, and disease progression. We develop a theoretical model of cellular organization in these tissues that takes into account more complex junctions between cells than previous models—junctions that provide insight into this stark difference in cell behavior.

Related Publication(s):

Disordered Photonic Materials

We design an amorphous material with a full photonic bandgap inspired by how cells pack in biological tissues. The size of the photonic bandgap can be manipulated through thermal and mechanical tuning. These directionally isotropic photonic bandgaps persist in solid and fluid phases, hence giving rise to a photonic fluid-like state that is robust with respect to fluid flow, rearrangements, and thermal fluctuations in contrast to traditional photonic crystals. This design should lead to the engineering of self-assembled nonrigid photonic structures with photonic bandgaps that can be controlled in real time via mechanical and thermal tuning.

Related Publication(s):

Mechnosensing and Mechanotransduction during wound healing

Many developmental processes involve collective cell motion, driven by migratory behaviors of individual cells and their interactions with the extracellular environment. An outstanding question is how cells regulate their internal driving forces to maintain tissue cohesiveness while promoting the requisite fluidity for collective motion. Progress has been limited by the lack of an integrative framework that couples cellular physical behavior with stochastic biochemical dynamics underlying cell motion and adhesion. Here we develop a cell-based computational model for collective cell migration during epithelial wound repair that integrates tissue mechanics with active cell motility, cell-substrate adhesions, and actomyosin dynamics. Using this model we show that an optimum balance of protrusive cell crawling and actomyosin contractility drives rapid directed motion of cohesive cell groups, robust to variations in cell and substrate physical properties. We further show that disparate modes of individual cell migration can cooperate to accelerate collective cell migration by fluidizing confluent tissues.

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