181 research outputs found
Membrane invagination induced by Shiga toxin B-subunit:From molecular structure to tube formation
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 (Gb(3)) 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 Gb(3) 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 Gb(3) lipids, our study points to a generic molecular design principle for clathrin-independent endocytosis of nanoparticles
The Role of Bilayer Tilt Difference in Equilibrium Membrane Shapes
Lipid bilayer membranes below their main transition have two tilt order
parameters, corresponding to the two monolayers. These two tilts may be
strongly coupled to membrane shape but only weakly coupled to each other. We
discuss some implications of this observation for rippled and saddle phases,
bilayer tubules, and bicontinuous phases. Tilt difference introduces a length
scale into the elastic theory of tilted fluid membranes. It can drive an
instability of the flat phase; it also provides a simple mechanism for the
spontaneous breaking of inversion symmetry seen in some recent experiments.Comment: Latex file; .ps available at
http://dept.physics.upenn.edu/~nelson/saddle.p
Escape from a metastable well under a time-ramped force
Thermally activated escape of an over-damped particle from a metastable well
under the action of a time-ramped force is studied. We express the mean first
passage time (MFPT) as the solution to a partial differential equation, which
we solve numerically for a model case. We discuss two approximations of the
MFPT, one of which works remarkably well over a wide range of loading rates,
while the second is easy to calculate and can provide a valuable first
estimate.Comment: 9 pages, including 2 figure
Validating a standardised test battery for synesthesia: Does the Synesthesia Battery reliably detect synesthesia?
Synesthesia is a neurological condition that gives rise to unusual secondary sensations (e.g., reading letters might trigger the experience of colour). Testing the consistency of these sensations over long time intervals is the behavioural gold standard assessment for detecting synesthesia (e.g., Simner, Mulvenna et al., 2006). In 2007 however, Eagleman and colleagues presented an online 'Synesthesia Battery' of tests aimed at identifying synesthesia by assessing consistency but within a single test session. This battery has been widely used but has never been previously validated against conventional long-term retesting, and with a randomly recruited sample from the general population. We recruited 2847 participants to complete The Synesthesia Battery and found the prevalence of grapheme-colour synesthesia in the general population to be 1.2%. This prevalence was in line with previous conventional prevalence estimates based on conventional long-term testing (e.g., Simner, Mulvenna et al., 2006). This reproduction of similar prevalence rates suggests that the Synesthesia Battery is indeed a valid methodology for assessing synesthesia. © 2015 The Authors
Rupture of multiple parallel molecular bonds under dynamic loading
Biological adhesion often involves several pairs of specific receptor-ligand
molecules. Using rate equations, we study theoretically the rupture of such
multiple parallel bonds under dynamic loading assisted by thermal activation.
For a simple generic type of cooperativity, both the rupture time and force
exhibit several different scaling regimes. The dependence of the rupture force
on the number of bonds is predicted to be either linear, like a square root or
logarithmic.Comment: 8 pages, 2 figure
A lattice model for the kinetics of rupture of fluid bilayer membranes
We have constructed a model for the kinetics of rupture of membranes under
tension, applying physical principles relevant to lipid bilayers held together
by hydrophobic interactions. The membrane is characterized by the bulk
compressibility (for expansion), the thickness of the hydrophobic part of the
bilayer, the hydrophobicity and a parameter characterizing the tail rigidity of
the lipids. The model is a lattice model which incorporates strain relaxation,
and considers the nucleation of pores at constant area, constant temperature,
and constant particle number. The particle number is conserved by allowing
multiple occupancy of the sites. An equilibrium ``phase diagram'' is
constructed as a function of temperature and strain with the total pore surface
and distribution as the order parameters. A first order rupture line is found
with increasing tension, and a continuous increase in proto-pore concentration
with rising temperature till instability. The model explains current results on
saturated and unsaturated PC lipid bilayers and thicker artificial bilayers
made of diblock copolymers. Pore size distributions are presented for various
values of area expansion and temperature, and the fractal dimension of the pore
edge is evaluated.Comment: 15 pages, 8 figure
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