A novel jamming phase diagram links tumor invasion to non-equilibrium phase separation.

It is well established that the early malignant tumor invades surrounding extracellular matrix (ECM) in a manner that depends upon material properties of constituent cells, surrounding ECM, and their interactions. Recent studies have established the capacity of the invading tumor spheroids to evolve into coexistent solid-like, fluid-like, and gas-like phases. Using breast cancer cell lines invading into engineered ECM, here we show that the spheroid interior develops spatial and temporal heterogeneities in material phase which, depending upon cell type and matrix density, ultimately result in a variety of phase separation patterns at the invasive front.

Geometric constraints during epithelial jamming.

As an injury heals, an embryo develops, or a carcinoma spreads, epithelial cells systematically change their shape. In each of these processes cell shape is studied extensively whereas variability of shape from cell-to-cell is regarded most often as biological noise. But where do cell shape and its variability come from? Here we report that cell shape and shape variability are mutually constrained through a relationship that is purely geometrical.

Scaling Physiologic Function from Cell to Tissue in Asthma, Cancer, and Development.

The formation of an integrated tissue from individual cells depends on the properties of the individual cells as well as the interaction of many cells acting as a collective. Three fundamental physiological processes govern the collective scaling from the individual cell to a working tissue: cell sorting, tissue assembly, and collective cellular migration. Mechanistically, cell sorting is governed by differential adhesion, whereas tissue assembly is controlled by the epithelial-to-mesenchymal transition and its inverse, the mesenchymal-to-epithelial transition.

Collective motion of mammalian cell cohorts in 3D.

Collective cell migration is ubiquitous in biology, from development to cancer; it occurs in complex systems comprised of heterogeneous cell types, signals and matrices, and requires large scale regulation in space and time. Understanding how cells achieve organized collective motility is crucial to addressing cellular and tissue function and disease progression. While current two-dimensional model systems recapitulate the dynamic properties of collective cell migration, quantitative three-dimensional equivalent model systems have proved elusive.

A quantitative comparison of human HT-1080 fibrosarcoma cells and primary human dermal fibroblasts identifies a 3D migration mechanism with properties unique to the transformed phenotype.

Here, we describe an engineering approach to quantitatively compare migration, morphologies, and adhesion for tumorigenic human fibrosarcoma cells (HT-1080s) and primary human dermal fibroblasts (hDFs) with the aim of identifying distinguishing properties of the transformed phenotype. Relative adhesiveness was quantified using self-assembled monolayer (SAM) arrays and proteolytic 3-dimensional (3D) migration was investigated using matrix metalloproteinase (MMP)-degradable poly(ethylene glycol) (PEG) hydrogels ("synthetic extracellular matrix" or "synthetic ECM"). In synthetic ECM, hDFs were characterized by vinculin-containing features on the tips of protrusions, multipolar morphologies, and organized actomyosin filaments.

Decoupling directed and passive motion in dynamic systems: particle tracking microrheology of sputum.

Probing the physical properties of heterogeneous materials is essential to understand the structure, function and dynamics of complex fluids including cells, mucus, and polymer solutions. Particle tracking microrheology is a useful method to passively probe viscoelastic properties on micron length scales by tracking the thermal motion of beads embedded in the sample. However, errors associated with active motion have limited the implementation to dynamic systems.

Nanomechanics of multiple units in the erythrocyte membrane skeletal network.

Erythrocytes undergo deformations when they transport O(2) and CO(2) across the membrane, yet the 3D nanomechanics of the skeletal network remains poorly understood. Expanding from our previous single isolated unit, we now simulate networks consisting of 1-10 concentric rings of repeating units in equibiaxial deformation. The networks are organized with (1) a 3D model for a single unit, (2) a wrap-around mode between Sp and actin protofilament in the intra-unit interaction, and (3) a random inter-unit connectivity.