No abstract

Recent results indicate that, in addition to chemical cues, mechanical stimuli may also impact neuronal growth. For instance, unlike most other cell types, neurons prefer soft substrates. However, the mechanisms responsible for the neuronal affinity for soft substrates have not yet been identified. In this study, we show that, in vitro, neurons continuously probe their mechanical environment. Growth cones visibly deform substrates with a compliance commensurate with their own. To understand the sensing of stiff substrates by growth cones, we investigated their precise temporal response to well-defined mechanical stress. When the applied stress exceeded a threshold of 274 +/- 41 pN/microm(2), neurons retracted and re-extended their processes, thereby enabling exploration of alternative directions. A calcium influx through stretch-activated ion channels and the detachment of adhesion sites were prerequisites for this retraction. Our data illustrate how growing neurons may detect and avoid stiff substrates--as a mechanism involved in axonal branch pruning--and provide what we believe is novel support of the idea that mechanics may act as guidance cue for neuronal growth.

We analyze the mechanical properties of three epithelial/mesenchymal cell lines (MCF-10A, MDA-MB-231, MDA-MB-436) that exhibit a shift in E-, N-and P-cadherin levels characteristic of an epithelial−mesenchymal transition associated with processes such as metastasis, to quantify the role of cell cohesion in cell sorting and compartmentalization. We develop a unique set of methods to measure cell-cell adhesiveness, cell stiffness and cell shapes, and compare the results to predictions from cell sorting in mixtures of cell populations. We find that the final sorted state is extremely robust among all three cell lines independent of epithelial or mesenchymal state, suggesting that cell sorting may play an important role in organization and boundary formation in tumours. We find that surface densities of adhesive molecules do not correlate with measured cell-cell adhesion, but do correlate with cell shapes, cell stiffness and the rate at which cells sort, in accordance with an extended version of the differential adhesion hypothesis (DAH). Surprisingly, the DAH does not correctly predict the final sorted state. This suggests that these tissues are not behaving as immiscible fluids, and that dynamical effects such as directional motility, friction and jamming may play an important role in tissue compartmentalization across the epithelial−mesenchymal transition. transgress even the strong lineage boundaries, invading adjacent tissues. Therefore, a question of immediate practical importance is what changes allow metastatic cells to break through these boundaries, or conversely, what prevents non-metastatic tumour cells from leaving the compartment? Moreover, it is a fundamental question if a solid tumour behaves sufficiently like a fluid that surface tension-like effects hold cancer cells back at the tumour boundary.Metastasis has been attributed to tumour cells losing epithelial characteristics and acquiring a more migratory mesenchymal phenotype [9][10][11]. This change known as the epithelial−mesenchymal transition (EMT) is typically accompanied by a loss of specific types of cellular adhesion. While epithelial cells are closely connected via various types of cell junctions such as adherens junctions and desmosomes that allow them to form organized cell layers in vivo and cell clusters in vitro, mesenchymal cells are less constrained, contacting only through focal points [11]. During EMT, the expression of E-cadherin decreases while the expression of N-cadherin and other cadherins increases [12][13][14]. This might be the molecular origin for the change in adhesiveness, although recent work highlights that different cadherins play vastly different roles in regulating intercellular forces and adhesion [15]. In addition, EMT also causes a down-regulation of the keratin cytoskeleton and a replacement with vimentin [16], which also hinders desmosome formation. This leads to secondary effects that modulate cell-cell adhesion. However, it remains unclear how these processes interact with boundary formation and compartment m...

Understanding the mechanics and dynamics of active matter at high density is indispensable to a range of physical and biological processes such as swarm dynamics, tissue formation and cancer metastasis. Here, we study the dynamics and mechanics of an MCF-10A epithelial cell monolayer on the multi-cellular and single-cell scales and over a wide density range. We show that the dynamics and Young's modulus of the monolayer are spatially heterogeneous on the multi-cellular scale. With increasing cell density, the monolayer approached kinetic arrest and the Young's modulus scaled critically. On the single-cell scale, as the cell density increased, cells were intermittently trapped in cages formed by their neighbors and their motion evolved from a ballistic motion to a sub-diffusive motion. Furthermore, the relaxation time and inverse self-diffusivity increased exponentially with the cell density. These findings provide a mechanism for long-ranged mechanical stress propagation, tissue remodeling and patterning at very high cell densities.

No abstract

Biomechanical properties are key to many cellular functions such as cell division and cell motility and thus are crucial in the development and understanding of several diseases, for instance cancer. The mechanics of the cellular cytoskeleton have been extensively characterized in cells and artificial systems. The rigidity of the plasma membrane, with the exception of red blood cells, is unknown and membrane rigidity measurements only exist for vesicles composed of a few synthetic lipids. In this study, thermal fluctuations of giant plasma membrane vesicles (GPMVs) directly derived from the plasma membranes of primary breast and cervical cells, as well as breast cell lines, are analyzed. Cell blebs or GPMVs were studied via thermal membrane fluctuations and mass spectrometry. It will be shown that cancer cell membranes are significantly softer than their non-malignant counterparts. This can be attributed to a loss of fluid raft forming lipids in malignant cells. These results indicate that the reduction of membrane rigidity promotes aggressive blebbing motion in invasive cancer cells.

No abstract

Biomechanical changes are critical for cancer progression.