Confinement energy landscape classification reveals membrane receptor nano-organization mechanisms Thursday, June 6, 2024 The cell membrane organization has an essential functional role through the control of membrane receptor confinement in micro- or nanodomains. Several mechanisms have been proposed to account for these properties, though some features have remained controversial, notably the nature, size, and stability of cholesterol- and sphingolipid-rich domains- or lipid rafts.Here, we probed the effective energy landscape actin on single nanoparticle-labeled membrane receptors confined in raft nanodomains - Epidermal Growth Factor, C. Read more
On the Response of Elongating Ribosomes to Forces Opposing Translocation Thursday, June 6, 2024 The elongation phase of protein synthesis is a cyclic, steady state process. It follows that its directionality is determined by the thermodynamics of the accompanying chemical reactions, which strongly favor elongation. Its irreversibility is guaranteed by its coupling to those reactions, rather being a consequence of any of the conformational changes that occur as it unfolds. It also follows that, in general, the rate of elongation is not proportional to the forward rate constants of any of its steps, including its final, mechano-chemical step, translocation. Read more
Varying the position of phospholipid acyl chain unsaturation modulates hopanoid and sterol ordering Thursday, June 6, 2024 The cell membrane must balance mechanical stability with fluidity to function as both a barrier and an organizational platform. Key to this balance is the ordering of hydrocarbon chains and packing of lipids. Many Eukaryotes synthesize sterols, which are uniquely capable of modulating lipid order to decouple membrane stability from fluidity. Ancient sterol analogues known as hopanoids are found in many bacteria and are proposed as ancestral ordering lipids. The juxtaposition of sterols and hopanoids in extant organisms prompts us to ask why both pathways persist, especially in light of their convergent ability to order lipids. Read more
Beyond stiffness: multiscale viscoelastic features as biomechanical markers for assessing cell types and states Monday, June 3, 2024 Cell mechanics are pivotal in regulating cellular activities, diseases progression, and cancer development. However, the understanding of how cellular viscoelastic properties varying in physiological and pathological stimuli remains scarce. Here, we develop a hybrid self-similar hierarchical theory-microrheology approach to accurately and efficiently characterize cellular viscoelasticity. Focusing on two key cell types associated with livers fibrosis − the capillarized liver sinusoidal endothelial cells (cLSEC) and activated hepatic stellate cells (aLX-2) − we uncover a universal two-stage power-law rheology characterized by two distinct exponents αshort and αlong. Read more
SANS reveals lipid-dependent oligomerization of an intramembrane aspartyl protease from H. volcanii Friday, May 31, 2024 Reactions that occur within the lipid membrane involve, at minimum, ternary complexes among the enzyme, substrate, and lipid. For many systems, the impact of the lipid in regulating activity or oligomerization state is poorly understood. Here we used small angle neutron scattering (SANS) to structurally characterize an intramembrane aspartyl protease (IAP), a class of membrane-bound enzymes that use membrane-embedded aspartate residues to hydrolyze transmembrane segments of biologically relevant substrates. Read more
Competing Mechanisms in Bacterial Invasion of Human Colon Mucus Probed with Agent-based Modeling Friday, May 31, 2024 The gastrointestinal tract is inhabited by a vast community of microorganisms, termed the gut microbiota. Large colonies can pose a health threat but the gastrointestinal mucus system protects epithelial cells from microbiota invasion. The human colon features a bilayer of mucus lining. Due to imbalances in intestinal homeostasis, bacteria may successfully penetrate the inner mucus layer which can lead to severe gut diseases. However, it is hard to tease apart the competing mechanisms that lead to this penetration. Read more
Shape of the membrane neck around a hole during plasma membrane repair Friday, May 31, 2024 Plasma membrane damage and rupture occurs frequently in cells and holes must be sealed rapidly to ensure homeostasis and cell survival. The membrane repair machinery is known to involve recruitment of curvature-inducing Annexin proteins, but the connection between membrane remodeling and hole closure is poorly described. The induction of curvature by repair proteins leads to the possible formation of a membrane neck around the hole as a key intermediate structure before sealing. We formulate a theoretical model of equilibrium neck shapes to examine the potential connection to a repair mechanism. Read more
Preserving condensate structure and composition by lowering sequence complexity Friday, May 31, 2024 Biomolecular condensates play a vital role in organizing cellular chemistry. They selectively partition biomolecules, preventing unwanted cross-talk and buffering against chemical noise. Intrinsically disordered proteins (IDPs) serve as primary components of these condensates due to their flexibility and ability to engage in multivalent interactions, leading to spontaneous aggregation. Theoretical advancements are critical at connecting IDP sequences with condensate emergent properties to establish the so-called molecular grammar. Read more
Effect of leaflet asymmetry on the stretching elasticity of lipid bilayers with phosphatidic acid Thursday, May 30, 2024 The asymmetry of membranes has a significant impact on their biophysical characteristics and behavior. This study investigates the composition and mechanical properties of symmetric and asymmetric membranes in giant unilamellar vesicles (GUVs) made of phosphatidylcholine (POPC) and phosphatidic acid (POPA). A combination of fluorescence quantification, zeta potential measurements, micropipette aspiration and bilayer molecular dynamics simulations are used to characterize these membranes. The outer leaflet composition in vesicles is found consistent across the two preparation methods we employed, namely electroformation and inverted emulsion transfer. Read more
Triacylglycerol-Droplet-Induced Bilayer Spontaneous Curvature in Giant Unilamellar Vesicles Thursday, May 30, 2024 This study investigated the incorporation of triacylglycerol droplets in the bilayers of giant unilamellar vesicles (GUVs) using four triacylglycerols and four phosphatidylcholines by confocal laser scanning microscopy. The triacylglycerol droplets were incorporated between the monolayer leaflets of the GUVs. Among the spherical droplets protruding on only one side of the bilayers, the droplets bound to the outer leaflets outnumbered those bound to the inner leaflets. The more frequent droplet binding to the outer leaflet caused transbilayer asymmetry in the droplet surface density. Read more
A multiscale sensorimotor model of experience-dependent behavior in a minimal organism Wednesday, May 29, 2024 To survive in ever-changing environments, living organisms need to continuously combine the ongoing external inputs they receive, representing present conditions, with their dynamical internal state, which includes influences of past experiences. It is still unclear in general, however 1) how this happens at the molecular and cellular levels and 2) how the corresponding molecular and cellular processes are integrated with the behavioral responses of the organism. Here, we address these issues by modeling mathematically a particular behavioral paradigm in a minimal model organism, namely chemotaxis in the nematode C. elegans. Read more
Cardiac length-dependent activation driven by force-dependent thick-filament dynamics Monday, May 27, 2024 The length-dependent activation (LDA) of maximum force and calcium sensitivity are established features of cardiac muscle contraction but the dominant underlying mechanisms remain to be fully clarified. Alongside the well documented regulation of contraction via the thin filaments, experiments have identified an additional force-dependent thick-filament activation, whereby myosin heads parked in a so-called “off” state become available to generate force. This process produces a feedback effect that may potentially drive LDA. Read more