Physical forces guide curvature sensing and cell migration mode bifurcating.

The ability of cells to sense and adapt to curvy topographical features has been implicated in organ morphogenesis, tissue repair, and tumor metastasis. However, how individual cells or multicellular assemblies sense and differentiate curvatures remains elusive. Here, we reveal a curvature sensing mechanism in which surface tension can selectively activate either actin or integrin flows, leading to bifurcating cell migration modes: focal adhesion formation that enables cell crawling at convex front edges and actin cable assembly that pulls cells forward at concave front edges.

The analytical solution to the migration of an epithelial monolayer with a circular spreading front and its implications in the gap closure process.

The coordinated behaviors of epithelial cells are widely observed in tissue development, such as re-epithelialization, tumor growth, and morphogenesis. In these processes, cells either migrate collectively or organize themselves into specific structures to serve certain purposes. In this work, we study a spreading epithelial monolayer whose migrating front encloses a circular gap in the monolayer center.

Spatiotemporal Oscillation in Confined Epithelial Motion upon Fluid-to-Solid Transition.

Fluid-to-solid phase transition in multicellular assembly is crucial in many developmental biological processes, such as embryogenesis and morphogenesis. However, biomechanical studies in this area are limited, and little is known about factors governing the transition and how cell behaviors are regulated. Due to different stresses present, cells could behave distinctively depending on the nature of tissue.

Actin-ring segment switching drives nonadhesive gap closure.

Gap closure to eliminate physical discontinuities and restore tissue integrity is a fundamental process in normal development and repair of damaged tissues and organs. Here, we demonstrate a nonadhesive gap closure model in which collective cell migration, large-scale actin-network fusion, and purse-string contraction orchestrate to restore the gap. Proliferative pressure drives migrating cells to attach onto the gap front at which a pluricellular actin ring is already assembled.

A traction force threshold signifies metastatic phenotypic change in multicellular epithelia.

Cancer metastasis has been believed as a genetically programmed process that is commonly marked by biochemical signals. Here using extracellular matrix control of cellular mechanics, we establish that cellular force threshold can also mark in vitro metastatic phenotypic change and malignant transformation in HCT-8 cell colonies. We observe that for prolonged culture time the HCT-8 cell colonies disperse into individual malignant cells, and the metastatic-like dispersion depends on both cell-seeding gel stiffness and colony size.

Mechanotargeting: Mechanics-Dependent Cellular Uptake of Nanoparticles.

Targeted delivery of nanoparticle (NP)-based diagnostic and therapeutic agents to malignant cells and tissues has exclusively relied on chemotargeting, wherein NPs are surface-coated with ligands that specifically bind to overexpressed receptors on malignant cells. Here, it is demonstrated that cellular uptake of NPs can also be biased to malignant cells based on the differential mechanical states of cells, enabling mechanotargeting. Owing to mechanotransduction, cell lines (HeLa and HCT-8) cultured on hydrogels of various stiffness are directed into different stress states, measured by cellular force microscopies.