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.

We report a method for the assay of proteins at concentrations lower than 10(-)(10) M with as little as 200 amol of protein. High sensitivity is accomplished by derivatizing the ε-amino group of the protein's lysine residues with the fluorogenic dye 5-furoylquinoline-3-carboxaldehyde and use of a sheath flow cuvette fluorescence detector. Most proteins have a large number of lysine residues; therefore, a large number of fluorescent molecules can be attached to each protein molecule. In general, precolumn labeling improves sensitivity but degrades resolution due to the inhomogeneity of the reaction products from multiple labeling. However, we demonstrate that, through careful manipulation of the separation and reaction conditions, high sensitivity can be obtained without excessive loss in separation efficiency. Over 190 000 theoretical plates are obtained for fluorescently labeled ovalbumin.

Two approaches were used to prepare a series of surface-modified capillaries. In the first, a sublayer was formed by coupling gamma-methacryloxypropyltrimethoxysilane to the surface silanol groups forming an SI-O bond; a top layer was then formed by polymerizing acrylamide in the capillary, which reacted with the sublayer. In the second approach, a sublayer was formed by silanol chlorination, followed by Grignard coupling of vinylmagnesium bromide to form an Si-C bond at the surface; a top layer was formed by polymerizing either acrylamide (AA), dimethylacrylamide (DMA), N-acryloylaminoethoxyethanol (AAEE), or N-acryloylaminopropanol (AAP) onto the sublayer. The Si-Cpoly(AA) capillaries were more stable and produced an approximately 10-fold lower electroosmotic flow compared to the Si-O-poly(AA) capillaries. The Si-C sublayer was used to compare the performance of all four top layers. Electroosmotic flow decreased in the order: Si-O-poly(AA), Si-C-poly(AA), Si-Cpoly(AAEE), Si-C-poly(DMA), and Si-C-poly(AAP). Si-C-poly(AA) showed evidence of irreversible degradation at pH 9 already after 40-50 runs. Si-C-polyAAP-coated capillaries demonstrated superior efficiency and migration time reproducibility for a number of alkaline proteins and for fluorescently labeled ovalbumin. Excellent performance was maintained, in the case of poly(AAP), for a least 300 runs (of 30 min duration) at pH 9.0.

Production and emission of CO2 from different sources have caused significant changes in the climate, which is the major concern related to global warming. Among other CO2 removal approaches, microalgae can efficiently remove CO2 through the rapid production of algal biomass. In addition, microalgae have the potential to be used in wastewater treatment. Although, wastewater treatment and CO2 removal by microalgae have been studied separately for a long time, there is no detailed information available on combining both processes. In this review article, microalgae-based CO2 biofixation, various microalgae cultivation systems,¯ and microalgae-derived wastewater treatment are separately discussed, followed by the concept of integration of CO2 biofixation process and wastewater treatment. In each section, details of energy efficiency and differences across microalgae species are also given.