INTRODUCTION-Along with its well-documented role as a track for cargo transport, the microtubule (MT) cytoskeleton is linked to diverse structural and signaling roles in the cardiac myocyte. MTs can facilitate the rapid transmission of mechanical signals to intracellular effectors, a process termed mechanotransduction. A proliferated MT network may also provide a mechanical resistance to cardiac contraction in certain disease states. Yet our understanding of how MTs resist compression and transmit mechanical signals has been impaired by a lack of direct observation and by the unpredictable effects of blunt pharmacological tools.

Physical changes in skin are among the most visible signs of aging. We found that young dermal fibroblasts secrete high levels of extracellular matrix (ECM) constituents, including proteoglycans, glycoproteins and cartilage-linking proteins. The most abundantly secreted was HAPLN1, a hyaluronic and proteoglycan link protein. HAPLN1 was lost in aged fibroblasts, resulting in a more aligned ECM that promoted metastasis of melanoma cells. Reconstituting HAPLN1 inhibited metastasis in an aged microenvironment, in 3D skin reconstruction models, and in vivo. Intriguingly, aged fibroblast-derived matrices had the opposite effects on the migration of T-cells, inhibiting their motility. HAPLN1 treatment of aged fibroblasts restored motility of mononuclear immune cells, while impeding that of polymorphonuclear immune cells, which in turn affected Treg recruitment. These data suggest while age-related physical changes in the ECM can promote tumor cell motility, they may adversely impact the motility of some immune cells, resulting in an overall change in the immune microenvironment. Understanding the physical changes in aging skin may provide avenues for more effective therapy for older melanoma patients.

Algae have several industrial applications that can lower the cost of biofuel co-23 production. Among these co-production applications, environmental and wastewater 24 bioremediation are increasingly important. Heavy metal pollution and its implications 25 for public health and the environment have led to increased interest in developing 26 environmental biotechnology approaches. We review the potential for algal biosorption 27 and/or neutralization of the toxic effects of heavy metal ions, primarily focusing on their 28 cellular structure, pretreatment, modification, as well as potential application of genetic 29 engineering in biosorption performance. We evaluate pretreatment, immobilization, and 30 factors affecting biosorption capacity, such as initial metal ion concentration, biomass 31 concentration, initial pH, time, temperature, and interference of multi metal ions and 32 introduce molecular tools to develop engineered algal strains with higher biosorption 33 capacity and selectivity. We conclude that consideration of these parameters can lead to 34 the development of low-cost micro and macroalgae cultivation with high bioremediation 35 potential. 36 37

Cancer cell invasion from primary tumors is mediated by a complex interplay between cellular adhesions, actomyosin-driven contractility, and the physical characteristics of the extracellular matrix (ECM). Here, we incorporate a mechanochemical free-energy-based approach to elucidate how the two-way feedback loop between cell contractility (induced by the activity of chemomechanical interactions such as Ca 2+ and Rho signaling pathways) and matrix fiber realignment and strain stiffening enables the cells to polarize and develop contractile forces to break free from the tumor spheroids and invade into the ECM. Interestingly, through this computational model, we are able to identify a critical stiffness that is required by the matrix to break intercellular adhesions and initiate cell invasion. Also, by considering the kinetics of the cell movement, our model predicts a biphasic invasiveness with respect to the stiffness of the matrix. These predictions are validated by analyzing the invasion of melanoma cells in collagen matrices of varying concentration. Our model also predicts a positive correlation between the elongated morphology of the invading cells and the alignment of fibers in the matrix, suggesting that cell polarization is directly proportional to the stiffness and alignment of the matrix. In contrast, cells in nonfibrous matrices are found to be rounded and not polarized, underscoring the key role played by the nonlinear mechanics of fibrous matrices. Importantly, our model shows that mechanical principles mediated by the contractility of the cells and the nonlinearity of the ECM behavior play a crucial role in determining the phenotype of the cell invasion.cell invasion | cell contractility | matrix realignment | Rho pathway | fibrous matrices C ell invasion into the surrounding matrix from nonvascularized primary tumors is the main mechanism by which cancer cells migrate to nearby blood vessels and metastasize to eventually form secondary tumors. This process is mediated by an intricate intercoupling between intracellular forces (such as cell contractility) and extracellular forces (adhesions and protrusions) that depend on the stiffness of the surrounding stroma and the alignment of matrix fibers. Previous experimental studies have examined the influence of these forces on the migratory behavior of cells during invasion. For example, the comparison between cell contractility in malignant and normal tissues has shown that the cells with malignant phenotype have a higher level of contractility (1-4). This elevated contractility is directly proportional to factors such as the stiffness of the extracellular matrix (ECM) and the fiber realignment (5-7), suggesting that the cross talk between ECM and intracellular contractility mediated by mechanosensory signaling pathways is also implicated in metastasis. Specifically, the activity of Rho, a myosin GTPase that regulates the activity of myosins, is elevated in proportion to the stiffness of the surrounding matrix (1,8,9), and inhibition of Rho-associated ...

The unique viscoelastic nature of axons is thought to underlie selective vulnerability to damage during traumatic brain injury. In particular, dynamic loading of axons has been shown to mechanically break microtubules at the time of injury. However, the mechanism of this rate-dependent response has remained elusive. Here, we present a microstructural model of the axonal cytoskeleton to quantitatively elucidate the interaction between microtubules and tau proteins under mechanical loading. Mirroring the axon ultrastructure, the microtubules were arranged in staggered arrays, cross-linked by tau proteins. We found that the viscoelastic behavior specifically of tau proteins leads to mechanical breaking of microtubules at high strain rates, whereas extension of tau allows for reversible sliding of microtubules without any damage at small strain rates. Based on the stiffness and viscosity of tau proteins inferred from single-molecule force spectroscopy studies, we predict the critical strain rate for microtubule breaking to be in the range 22-44 s(-1), in excellent agreement with recent experiments on dynamic loading of micropatterned neuronal cultures. We also identified a characteristic length scale for load transfer that depends on microstructural properties and have derived a phase diagram in the parameter space spanned by loading rate and microtubule length that demarcates those regions where axons can be loaded and unloaded reversibly and those where axons are injured due to breaking of the microtubules.