Mutations to WNT ligands in cancer are poorly understood. WNT ligands are a family of secreted proteins that trigger the activation of the WNT pathway with essential roles in cell development and carcinogenesis, particularly of the colorectal tract. Whilst the structure of WNT ligands has been elucidated, little is known about how mutations in these proteins affect colorectal cancer. Here we show that

Characterizing the function of force-gated ion channels is essential for understanding their molecular mechanisms and how they are affected by disease-causing mutations, lipids, or small molecules. Pressure-clamp electrophysiology is a method that is established and widely used to characterize the mechanical sensitivity of force-gated ion channels. However, the physical stimulus many force-gated ion

Single-molecule spectroscopy combined with Förster resonance energy transfer (FRET) is widely used to quantify distance dynamics and distributions in biomolecules. Most commonly, measurements are interpreted using simple analytical relations between experimental observables and the underlying distance distributions. However, these relations make simplifying assumptions, such as a separation of timescales

In many quantitative investigations of biological systems, including, e.g., the study of biomolecular interactions, assembly and disassembly, aggregation, micelle and vesicle formation or drug encapsulation, accurate determination of particle sizes is of key interest. Fluorescence Correlation Spectroscopy (FCS) with its exceptional sensitivity for molecular diffusion properties has long been proposed

Infrared neural stimulation (INS) uses transient near-infrared light to activate neuronal activity, likely through heat-induced thermal gradients. However, neither the effect of basal temperature nor heat accumulation has specifically been investigated. This study examines how spatial temperature gradients, varied by different laser repetition rates and the addition of a continuous wave (CW) laser

Solid-state nuclear magnetic resonance (ssNMR) is a powerful technique for studying membrane protein structure and dynamics. Ideally, measurements are performed with the protein in a lipid bilayer. However, homogenous reconstitution of functional protein into intact bilayers at sufficiently high concentrations is often difficult to achieve. In this work, we investigate the suitability of the lipid

Natriuretic peptides are produced predominantly by atrial cardiomyocytes in response to cardiovascular stress and attenuate cardiac maladaptation by reducing blood pressure, blood volume, and cardiac workload primarily through activation of natriuretic peptide receptors in the kidney and vasculature. However, mechanisms underlying cardiomyocyte exocytosis and natriuretic peptide secretion remain poorly

Measurements of cell size dynamics have revealed phenomenological principles by which individual cells control their size across diverse organisms. One of the emerging paradigms of cell size homeostasis is the adder, where the cell cycle duration is established such that the cell size increase from birth to division is independent of the newborn cell size. We provide a mechanistic formulation of the

For several decades, many attempts have been made to characterize the mechanical properties of gray and white matter, which constitute the two main compartments of the central nervous system, with various methods and contradictory results. In particular, the ratio of gray/white matter elasticity is sometimes larger than 1 and sometimes smaller; the reason for this apparent discrepancy is currently

The deformation of red blood cells (RBCs) in Poiseuille flows of capillary vessels is fundamental for hemodynamics in cellular scale for various physiological or pathological scenarios. However, the mechanical criterion for membrane buckling and the impact of the asymmetric deformations of cells on the hemodynamics are currently unclear. In this study, a microfluidic system with narrow tubular channels

The aggregation of red blood cells (RBCs) is a complex phenomenon that strongly impacts blood flow and tissue perfusion. Despite extensive research for more than 50 years, physical mechanisms that govern RBC aggregation are still under debate. Two proposed mechanisms are based on bridging and depletion interactions between RBCs due to the presence of macromolecules in blood plasma. The bridging hypothesis

The single-molecule biophysics community has delivered significant impacts to our understanding of fundamental biological processes, yet the field is also siloed and has fragmented data structures, which impede data sharing and limit the ability to conduct comprehensive meta-analyses. To advance the field of optical tweezers in single-molecule biophysics, it is important that the field adopts open

During development and wound healing, cells need to form long-range ordered structures to ensure precise formation of organs and repair damage. This requires cells to locate specific partner cells to which to adhere. How such cell matching reliably happens is an open problem, particularly in the presence of biological variability. Here, we use an equilibrium energy model to simulate how cell matching

The Halbach array, originally developed for particle accelerators, is a compact arrangement of permanent magnets that creates well-defined magnetic fields without heating. Here, we demonstrate its use for modulating the speed of electromechanical waves in cardiac syncytia of human stem cell-derived cardiomyocytes. At 40–50 mT magnetic field strength, a cylindrical dipolar Halbach array boosted the

Measuring co-localization of different types of molecules is essential to understand molecular organization in biological systems. The pair cross-correlation (PCC) function computed from two-color microscopy images provides a measure of co-localization between differently labeled molecules. Here, we compute a theoretical expression for the PCC function between two molecules using two-dimensional Gaussian

Electrotaxis, the process by which eukaryotic cells establish polarity and move directionally along an electric field, is a well-studied mechanism to steer the migration of cells in vitro and in vivo. Although the influence of an electric field on single cells in culture is well documented, the influence of the electric field on cell-cell interactions has not been well studied. In this work, we quantify

α-hemolysin (HlyA) is a major exotoxin secreted by uropathogenic Escherichia coli (UPEC), known for its ability to lyse red blood cells (RBCs). Although its lytic effects are well characterized, the nonlytic alterations on RBCs, such as increased permeability to Ca2+, osmotic imbalance, and morphological alterations, remain less understood and may be critical in UPEC pathogenesis. This study investigates

Vitamin E (VE) has historically been described as an antioxidant and its roles in radical species scavenging and nutrition are well studied. VE has been proposed to have secondary roles within the membrane but these roles are not as well characterized, with contradictory results emerging throughout the literature. Due to similar structural motifs, comparisons between VE and cholesterol (CHO), another

As a sound pressure detector that uses energy to boost both its sensitivity and selectivity, the inner ear is an active nonequilibrium system. The collective processes of the inner ear that give rise to this exquisite functionality remain poorly understood. One manifestation of the active ear across the animal kingdom is the presence of spontaneous otoacoustic emission (SOAE), idiosyncratic arrays

Accurate estimation of the strength of the protein-ligand interaction is important in the field of drug discovery. The binding strength can be determined by using experimental binding affinity assays which are both time and labor consuming and costly. Predicting the binding affinity/energy in silico is an alternative approach, particularly for virtual screening of large data sets. In general, the distance-based

Interfacial hydrogen bonding (H-bonding) partly determines membrane structure, heterogeneity, and dynamics. Given the chemical diversity of lipids, it is important to understand how composition determines lipid-lipid interactions and how those are translated to H-bond populations and dynamics. Here, we investigate the role of palmitoyl sphingosylphosphorylcholine (PSM) in modulating lipid H-bond networks

Nicotinic acetylcholine receptors (nAChRs) are critical ligand-gated ion channels in the human nervous system. They are targets for various neurotoxins produced by algae, plants, and animals. While many structures of nAChRs bound by neurotoxins have been published, the binding mechanism of toxins to the nAChRs remains unclear. In this work, we have performed extensive Gaussian accelerated molecular

The molecular interactions between a fungal membrane model and SJGAP, a 32-amino-acid antimicrobial peptide (AMP) derived from skipjack tuna GAPDH, as well as four analogs, were investigated using molecular dynamics simulations and Fourier transform infrared (FTIR) spectroscopy. In a previous study, Analog 7, modified by replacing three alanine residues with leucine residues, exhibited unique antifungal

Phosphatidylinositides constitute only 1%–3% of plasma membranes but play vital roles in cellular signaling. In particular, phosphatidylinositol 4,5-bisphosphate (PIP2) is involved in processes such as cytoskeleton organization and ion-channel regulation. Pleckstrin homology (PH) domains are modular domains found in many proteins and are known for their strong affinity for PIP2 headgroups. The role

Single-molecule localization microscopy (SMLM) has revolutionized the understanding of cellular organization by reconstructing informative images with quantifiable spatial distributions of molecules far beyond the optical diffraction limit. Much effort has been devoted to optimizing localization accuracy. One such approach is the assessment of SMLM data quality in real time rather than after lengthy

The human genome consists of about 2 m of DNA packed inside the cell nucleus barely 10 μm in diameter. DNA is complexed with histones, forming chromatin fiber, which folds inside the nucleus into loops, topologically associating domains, A/B compartments, and chromosome territories. This organization is knot-free and self-similar across length scales, leading to a hypothesis that the genome presents

Super-resolution light microscopy techniques facilitate the observation of nm-sized biomolecules, which are 1–2 orders of magnitude smaller than the diffraction limit of light. Using super-resolution microscopy techniques, it is possible to observe fluorescence from two biomolecules in close proximity; however, not necessarily in direct interaction. Using FRETsael, we localize biomolecular interactions

Humans have three known ATP-binding cassette (ABC) transporters in the inner mitochondrial membrane (ABCB7, ABCB8, and ABCB10). ABCB10, the most studied of them thus far, is essential for normal red blood cell development and protection against oxidative stress, and it was recently found to export biliverdin, a heme degradation product with antioxidant properties. The molecular mechanism underlying

The Fat/Dachsous (Ft/Ds) pathway is a highly conserved pathway regulating planar cell polarity (PCP) across different animal species. Proteins from the Ft and Ds family are large transmembrane protocadherins that form heterophilic complexes on the boundaries between cells. Fat4 and Dchs1, the main mammalian homologs of this pathway, have been implicated in PCP in various epithelial tissues and were