Research
I use theoretical and computational models to understand how biological tissues deform, flow, and maintain integrity — with connections to development, disease, and the physics of disordered materials.
Tissue Plasticity & Avalanches
During development and under normal physiological conditions, biological tissues are continuously subjected to substantial mechanical stresses. In response to large deformations, cells must undergo multicellular rearrangements to maintain tissue integrity and robustness. How these events are connected in time and space, however, remains unknown.
Using theoretical modeling, we study the mechanical plasticity of cell monolayers under large deformations. Our results suggest that the jamming–unjamming (solid–fluid) transition can vary significantly depending on the degree of deformation, implying that tissues are highly unconventional materials. We also demonstrate how large deformations are accommodated through a series of cellular rearrangements — analogous to avalanches in non-living disordered materials.
We find that these "tissue avalanches" are governed by stress redistribution and the spatial distribution of soft or vulnerable spots that are more prone to rearrangement. Finally, we propose a simple, experimentally accessible framework to infer tissue-level stress and predict avalanches from static images alone.
Vertex model simulation showing tissue rearrangements under shear deformation
Cell–Cell Adhesion · Tissue Fluidity · Viscoelasticity
Cell–Cell Adhesion as a Double-Edged Sword in Tissue Fluidity
Cell–cell adhesion is widely regarded as a rigidity-promoting "biological glue." Our work reveals a more nuanced picture: adhesion acts through two competing channels with opposite effects on tissue fluidity.
The energetic contribution — cadherin bonds reducing effective junctional tension — softens cells and lowers the barrier to neighbor exchange, promoting fluidity. The viscous-dissipative contribution — frictional resistance generated by bond turnover during junctional remodeling — opposes cell rearrangements and drives the tissue toward arrest. Together, they produce a non-monotonic jamming phase diagram: increasing adhesion can either fluidize or jam a tissue depending on which channel dominates.
A key prediction is shape-independent fluidization — tissue dynamics can change dramatically with no change in cell geometry. Experiments on MDCK monolayers confirm this: blocking E-cadherin increases fluidity sixfold while leaving cell shape, junctional tension, and substrate traction unchanged. The videos illustrate this effect directly.
Control — untreated MDCK monolayer
DECMA-1 (7.5 µg mL⁻¹) — E-cadherin blocked, tissue fluidized with no change in cell shape
Tissue Response to Compression
Cellular unjamming — the collective fluidization of cell motion — has been linked to many biological processes, including development, wound repair, and tumor growth. However, because multiple cellular and molecular mechanisms may operate simultaneously, the role of compressive stress in unjamming transitions remains poorly understood.
We investigate which mechanism dominates in a dense, mechanically stressed monolayer. Long-term compression triggers cell arrest in benign epithelial cells while enhancing cancer cell migration — transitions correlated with cell shape. We find that cadherin-mediated cell–cell adhesion regulates these differential responses and is an important driver of unjamming in stressed monolayers.
Importantly, compressive stress does not induce epithelial–mesenchymal transition in unjammed cells. Traction force microscopy further reveals the attenuation of traction stresses in compressed cells within the bulk monolayer regardless of cell type. Together, strengthened intercellular adhesion and attenuated traction forces lead to tissue fluidization and may impact collective motion in breast cancer progression.
MCF10A epithelial cells — normal condition
MCF10A epithelial cells — under vertical compression