The bacterial Shiga toxin is composed of an enzymatically active A-subunit, and a receptor-binding homopentameric B-subunit (STxB) that mediates intracellular toxin trafficking. Upon STxB-mediated binding to the glycolipid globotriaosylceramide (Gb3) at the plasma membrane of target cells, Shiga toxin is internalized by clathrin-dependent and independent endocytosis. The formation of tubular membrane invaginations is an essential step in the clathrin-independent STxB uptake process. However, the mechanism by which STxB induces these invaginations has remained unclear. Using a combination of all-atom molecular dynamics and Monte Carlo simulations we show that the molecular architecture of STxB enables the following sequence of events: the Gb3 binding sites on STxB are arranged such that tight avidity-based binding results in a small increment of local curvature. Membrane-mediated clustering of several toxin molecules then creates a tubular membrane invagination that drives toxin entry into the cell. This mechanism requires: (1) a precise molecular architecture of the STxB binding sites; (2) a fluid bilayer in order for the tubular invagination to form. Although, STxB binding to the membrane requires specific interactions with Gb3 lipids, our study points to a generic molecular design principle for clathrin-independent endocytosis of nanoparticles.

There are more than 2 million bone grafting procedures performed annually in US alone. Despite significant efforts, the repair of large segmental bone defects is a substantial clinical challenge which...

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Stress responses in both plants2؉ transient and survival of cultures subjected to NaCl stress was similar for the ACA2 transformant and K601. However, whereas K601 maintained low cytosolic Na ؉ predominantly by pumping it out across the plasma membrane, the transformant sequestered Na ؉ in internal organelles. This sequestration requires the presence of an endomembrane Na ؉ /H ؉ -antiporter, NHX1, which does not play a significant role in salt tolerance of wild type yeast except at acidic pH. Transcript levels of the plasma membrane Na ؉ -ATPase, ENA1, were strongly induced only in K601, whereas NHX1 was strongly induced in both K601 and the ACA2 transformant. The calmodulin kinase inhibitor KN62 significantly reduced the salt tolerance of the ACA2 transformant and the transcriptional induction of NHX1. Thus, the heterologous expression of a plant endomembrane Ca 2؉ pump results in the rapid depletion of cytosolic Ca 2؉ and the activation of an alternate mechanism for surviving saline stress.

Polymeric electrospun fibers have the potential to be utilized for a variety of applications such as tissue engineering, filtration, and textiles, owing to their high surface area per unit mass. However, these applications have some form of dependency on the mechanical properties of fiber meshes. Therefore, the current study is aimed at understanding the mechanical behavior of electrospun fiber systems at different length scales in order to establish a correlation between their structure and mechanical properties. Micro‐/nano‐fiber meshes of polystyrene were fabricated by the process of electrospinning and were subjected to uniaxial tensile testing. High‐resolution imaging during tensile testing revealed the macroscopic and microscopic structural evolution of these fibers. Further, the dependence of tensile strength, % elongation, and toughness of fiber meshes on the orientation of the fibers were also experimentally observed. The continuum mechanics simulation studies of fiber meshes with different orientations corroborated well with these experimental studies. Comprehensively, these studies demonstrated the changes in mechanical behavior of electrospun fiber meshes owing to the reorientation and alignment of fibers in meshes at microscopic and macroscopic length scale during tensile testing. Such study can be extrapolate for the design and fabrication of load‐bearing tissues scaffolds, and filtration devices. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 45012.