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Bladder, colon, gastric, prostate, and uterine cancers originate in organs surrounded by laminin coated smooth muscle. In human prostate cancer, tumors that are organ-confined, without extracapsular extension (ECE) through muscle, have an overall cancer survival rate of up to 97% as compared to 32% for metastatic disease. Our previous work modeling ECE reported the blocking of tumor invasion by mutation of a laminin-binding integrin called α6β1. Expression of the α6AA mutant resulted in a biophysical switch from cell-ECM (extracellular matrix) to cell-cell adhesion with drug sensitivity properties and an inability to invade muscle.

The advancement of single-channel level recording via the patch clamp technique has provided a powerful means of assessing the detailed behaviors of various types of ion channels in native and exogenously expressed cellular environments. However, such recordings of gap junction (GJ) channels are hampered by unique challenges that are related to their unusual intercellular configuration and natural clustering into densely-packed plaques. Thus, the methods for reliable cross-correlation of data recorded at macroscopic and single channel levels are lacking in studies of GJs.

The properties of a potentiator are typically evaluated by measuring its ability to enhance the magnitude of the control response. Analysis of the ability of drugs to potentiate responses from receptor-channels takes place in the context of particular models to extract parameters for functional effects. In the often-used co-agonist model, the agonist generating control activity and the potentiator enhancing the control activity make additive energetic contributions to stabilize the active state of the receptor.

Here we investigate how a subpopulation of cells can move through an aggregate of cells. Using a stochastic force-based model of Dictyostelium discoideum when the population is forming a slug, we simulate different strategies for prestalk cells to reliably move to the front of the slug while omitting interaction with the substrate thus ignoring the overall motion of the slug. Of the mechanisms that we simulated, prestalk cells being more directed is the best strategy followed by increased asymmetric motive forces for prestalk cells.

The most effective tested optogenetic tools available for neuronal silencing are the light-gated anion channel proteins found in the cryptophyte alga Guillardia theta (GtACRs). Molecular mechanisms of GtACRs, including the photointermediates responsible for the open channel state, are of great interest for understanding their exceptional conductance. In this study, the photoreactions of GtACR1 and its D234N, A75E and S97E mutants were investigated using multichannel time-resolved absorption spectroscopy.

Liquid-liquid phase separation (LLPS) inside the cell often results in biological condensates that can critically impact cell homeostasis. Such phase separation events occur in multiple parts of cells, including the cell membranes, where the so-called “lipid raft” hypothesis posits the formation of ordered domains floating in a sea of disordered lipids. The resulting lipid domains often have functional roles. However, the thermodynamics of lipid phase separation and their resulting mechanistic effects on cell function and dysfunction are poorly understood.

Caveolins form complexes of various sizes that deform membranes into polyhedral shapes. However, the recent structure of the 8S complex was disk-like with a flat membrane-binding surface. How can a flat complex deform membranes into nonplanar structures? Molecular dynamics simulations revealed that the 8S complex rapidly takes the form of a suction cup. Simulations on implicit membrane vesicles determined that binding is stronger when E140 gets protonated. In that case, the complex binds much more strongly to 5 and 10-nm radius vesicles.

Plasma membrane induced protein folding and conformational transitions play a central role in cellular homeostasis. Several transmembrane proteins are folded in the complex lipid milieu to acquire a specific structure and function. Bacterial pore forming toxins (PFTs) are proteins expressed by a large class of pathogenic bacteria that exploit the plasma membrane environment to efficiently undergo secondary structure changes, oligomerize, and form transmembrane pores. Unregulated pore formation causes ion imbalance, leading to cell death and infection.

The activity of many membrane receptors is controlled through their lateral association into dimers or higher order oligomers. While Förster resonance energy transfer (FRET) measurements have been used extensively to characterize the stability of receptor dimers, the utility of FRET in studies of larger oligomers has been limited. Here we introduce an effective equilibrium dissociation constant that can be extracted from FRET measurements for EphA2, a receptor tyrosine kinase (RTK) known to form active oligomers of heterogeneous distributions in response to its ligand ephrinA1-Fc.

Fluorescent lipid probes are an invaluable tool for investigating lipid membranes. In particular, localizing particular receptor lipids such as glycosphingolipids within phase-separated membranes is of pivotal interest to understanding the influence of protein-receptor lipid binding on membrane organization. However, fluorescent labeling can readily alter the phase behavior of a lipid membrane because of the interaction of the fluorescent moiety with the membrane interface. Here, we investigated Gb3 glycosphingolipids, serving as receptor lipids for the protein Shiga toxin, with a headgroup attached BODIPY fluorophore separated by a polyethylene glycol (PEG) spacer of different lengths.

Lysophospholipids (lysoPLs) are crucial metabolites involved in various physiological and pathological cellular processes. Understanding their binding interactions, particularly with human serum albumin (HSA), is essential due to their role in regulating lysoPLs-induced cytotoxicity. However, the precise mechanism of lysoPLs binding to HSA remains elusive. In this study, we employed fluorescence quenching and optical interferometry assays to demonstrate direct binding between lysophosphatidylcholine (LPC) and HSA (KRDR= 25 μM).

Macromolecular solubility is an important contributor to the driving forces for phase separation. Formally, the driving forces in a binary mixture comprising a macromolecule dissolved in a solvent can be quantified in terms of the saturation concentration, which is the threshold macromolecular concentration above which the mixture separates into coexisting dense and dilute phases. Additionally, the second virial coefficient, which measures the effective strength of solvent-mediated intermolecular interactions provides direct assessments of solvent quality.