Traction Force Microscopy (TFM) has emerged as a widely used standard methodology to measure cell-generated traction forces and determine their role in regulating cell behavior. While TFM platforms have enabled many discoveries, their implementation remains limited due to complex experimental procedures, specialized substrates, and the ill-posed inverse problem where low magnitude high-frequency noise in the displacement field severely contaminates the resulting traction measurements. Here, we introduce Deep Morphology Traction Microscopy (DeepMorphoTM), a Deep Learning alternative to conventi ..read more

Cells in developing embryos must make multiple decisions about their fate, migration, and polarity to ensure proper tissue growth, morphogenesis, and function specification. These decisions are determined by the positions of cells within the tissue. It is often proposed that proteins called morphogens spread throughout the tissue, establishing concentration gradients that are subsequently read by specific receptors on the cell surface to transfer positional information. Various models have been proposed to explain how such gradients can robustly transfer information at distances in a growing t ..read more

The voltage-gated K+ channel, hERG, is a member of the Ether-a-go-go family and plays a critical role in heart physiology by repolarizing cardiac myocytes (1-4). The functional channel is comprised of four subunits, each including six transmembrane domains with large intracellular domains, a Per-ARNT-Sim (PAS) domain in the amino terminus, and the cyclic nucleotide-binding homology domain (CNBHD) in the carboxy terminus. Interactions between the PAS domain and CNBHD have been implicated in hERG channel deactivation (5-7), but these domains interact during channel gating remains largely unknown ..read more

Protein-DNA interactions and protein-mediated DNA compaction play key roles in a range of biological processes. The length scales typically involved in DNA bending, bridging, looping, and compaction (≥ 1 kbp) are challenging to address experimentally or by all-atom molecular dynamics simulations, making coarse-grained simulations a natural approach. Here we present a simple and generic coarse-grained model for the DNA-protein and protein-protein interactions, and investigate the role of the latter in the protein-induced compaction of DNA ..read more

It is important to understand the behaviours of fluorescent molecules because, firstly, they are often utilized as probes in biophysical experiments and, secondly, they are crucial cofactors in biological processes such as photosynthesis. A phenomenon called “fluorescence quenching” occurs when fluorophores are present at high concentrations but the mechanisms for quenching are debated. Here, we used a technique called “in-membrane electrophoresis” to generate concentration gradients of fluorophores within a supported lipid bilayer (SLB), across which quenching was expected to occur ..read more

Morphogens are intercellular signaling molecules providing spatial information to cells in developing tissues to coordinate cell fate decisions. The spatial information is encoded within long-ranged concentration gradients of the morphogen. Direct measurement of morphogen dynamics in a range of systems suggests that local and global diffusion coefficients can differ by orders of magnitude. Further, local diffusivity can be large, which would potentially abolish any concentration gradient rapidly ..read more

Insulin levels in the blood oscillate with a variety of periods, including rapid ( 5 – 10 min), ultradian (50 – 120 min), and circadian (24 h). Oscillations of insulin are beneficial for lowering blood glucose and disrupted rhythms are found in people with type 2 diabetes and their close relatives. These in vivo secretion dynamics imply that the oscillatory activity of individual islets of Langerhans are synchronized, although the mechanism for this is not known. One mechanism by which islets may synchronize is negative feedback of insulin on whole body glucose levels ..read more

Proton transport across lipid membranes is one of the most fundamental reactions that make up living organisms. , however, the study of proton transport reactions can be very challenging due to limitations imposed by proton concentrations, compartment size, and unstirred layers as well as buffer exchange and buffer capacity. In this study, we have developed a proton permeation assay based on the microfluidic trapping of giant vesicles enclosing the pH-sensitive dye pyranine to address some of these challenges ..read more

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Protein solutions can undergo liquid-liquid phase separation (LLPS), where a dispersed phase with a low protein concentration coexists with coacervates with a high protein concentration. We focus on the low complexity N-terminal domain of cytoplasmic polyadenylation element binding-4 protein, CPEB4 , and its isoform depleted of the Exon4, CPEB4Δ4 . They both exhibit LLPS, but in contrast to most systems undergoing LLPS, the single-phase regime preceding LLPS consists mainly of soluble protein clusters ..read more