HLA3DB: comprehensive annotation of peptide/HLA complexes enables blind structure prediction of T cell epitopes.

The class I proteins of the major histocompatibility complex (MHC-I) display epitopic peptides derived from endogenous proteins on the cell surface for immune surveillance. Accurate modeling of peptides bound to the human MHC, HLA, has been mired by conformational diversity of the central peptide residues, which are critical for recognition by T cell receptors. Here, analysis of X-ray crystal structures within our curated database (HLA3DB) shows that pHLA complexes encompassing multiple HLA allotypes present a discrete set of peptide backbone conformations.

HLA3DB: comprehensive annotation of peptide/HLA complexes enables blind structure prediction of T cell epitopes.

The class I proteins of the major histocompatibility complex (MHC-I) display epitopic peptides derived from endogenous proteins on the cell surface for immune surveillance. Accurate modeling of peptide/HLA (pHLA, the human MHC) structures has been mired by conformational diversity of the central peptide residues, which are critical for recognition by T cell receptors. Here, analysis of X-ray crystal structures within a curated database (HLA3DB) shows that pHLA complexes encompassing multiple HLA allotypes present a discrete set of peptide backbone conformations.

Biophysical Considerations in the Rational Design and Cellular Targeting of Flexible Polymeric Nanoparticles.

How nanoparticle (NP) mechanical properties impact multivalent ligand-receptor-mediated binding to cell surfaces, the avidity, propensity for internalization, and effects due to crowding remains unknown or unquantified. Through computational analyses, the effects of NP composition from soft, deformable NPs to rigid spheres, effect of tethers, the crowding of NPs at the membrane surface, and the cell membrane properties such as cytoskeletal interactions are addressed. Analyses of binding mechanisms of three distinct NPs that differ in type and rigidity (core-corona flexible NP, rigid NP, and rigid-tethered NP) but are otherwise similar in size and ligand surface density are reported; moreover, for the case of flexible NP, NP stiffness is tuned by varying the internal crosslinking density.

Crowding-induced membrane remodeling: Interplay of membrane tension, polymer density, architecture.

The plasma membrane hosts a wide range of biomolecules, mainly proteins and carbohydrates, that mediate cellular interactions with its environment. The crowding of such biomolecules regulates cellular morphologies and cellular trafficking. Recent discoveries have shown that the structure and density of cell surface polymers and hence the signaling machinery change with the state of the cell, especially in cancer progression.

Probing lipid membrane bending mechanics using gold nanorod tracking.

Lipid bilayer membranes undergo rapid bending undulations with wavelengths from tens of nanometers to tens of microns due to thermal fluctuations. Here, we probe such undulations and the membranes' mechanics by measuring the time-varying orientation of single gold nanorods (GNRs) adhered to the membrane, using high-speed dark field microscopy. In a lipid vesicle, such measurements allow the determination of the membrane's viscosity, bending rigidity, and tension as well as the friction coefficient for sliding of the monolayers over one another.

Dimerization and structure formation of colloids via capillarity at curved fluid interfaces.

Capillary interactions are ubiquitous between colloids trapped at fluid interfaces. Generally, colloids in fluid interfaces have pinned, undulated contact lines that distort the interface around them. To minimize the area, and therefore the energy of these distortions, colloids interact and assemble in a manner that depends on the shape of the host interface.

A multiscale biophysical model for the recruitment of actin nucleating proteins at the membrane interface.

The dynamics and organization of the actin cytoskeleton are crucial to many cellular events such as motility, polarization, cell shaping, and cell division. The intracellular and extracellular signaling associated with this cytoskeletal network is communicated through cell membranes. Hence the organization of membrane macromolecules and actin filament assembly are highly interdependent.

Emergent membrane morphologies in relaxed and tense membranes in presence of reversible adhesive pinning interactions.

The morphologies of cell membranes, and specifically the local curvature distributions are determined either by its intrinsic components such as lipids and membrane-associated proteins or by the adhesion forces due to membrane interactions with the cytoskeleton, extracellular matrix (ECM) and other cells in the tissue, as well as physical variables such as membrane and frame tensions. We present a computational analysis for a model of pinned membranes based on the dynamically triangulated Monte Carlo (MC) model for membranes. We show that membrane adhesion to ECM or a substrate promotes curvature generation on cell membranes, and this process depends on the excess area, or equivalently membrane tension, and the density of adhesion sites.

Lateral distribution of phosphatidylinositol 4,5-bisphosphate in membranes regulates formin- and ARP2/3-mediated actin nucleation.

Spatial and temporal control of actin polymerization is fundamental for many cellular processes, including cell migration, division, vesicle trafficking, and response to agonists. Many actin-regulatory proteins interact with phosphatidylinositol 4,5-bisphosphate (PI(4,5)P) and are either activated or inactivated by local PI(4,5)P concentrations that form transiently at the cytoplasmic face of cell membranes. The molecular mechanisms of these interactions and how the dozens of PI(4,5)P-sensitive actin-binding proteins are selectively recruited to membrane PI(4,5)P pools remains undefined.