SARS-CoV-2 rate of spread in and across tissue, groundwater and soil: A meshless algorithm for the fractional diffusion equation.

The epidemiological aspects of the viral dynamic of the SARS-CoV-2 have become increasingly crucial due to major questions and uncertainties around the unaddressed issues of how corpse burial or the disposal of contaminated waste impacts nearby soil and groundwater. Here, a theoretical framework base on a meshless algorithm using the moving least squares (MLS) shape functions is adopted for solving the time-fractional model of the viral diffusion in and across three different environments including water, tissue, and soil. Our computations predict that by considering the α (order of fractional derivative) best fit to experimental data, the virus has a traveling distance of 1 m m in water after 22, regardless of the source of contamination (e.g., from tissue or soil). The outcomes and extrapolations of our study are fundamental for providing valuable benchmarks for future experimentation on this topic and ultimately for the accurate description of viral spread across different environments. In addition to COVID-19 relief efforts, our methodology can be adapted for a wide range of applications such as studying virus ecology and genomic reservoirs in freshwater and marine environments.

Origin of the Force: The Force-From-Lipids Principle Applied to Piezo Channels.

Piezo channels are a ubiquitously expressed, principal type of molecular force sensor in eukaryotes. They enable cells to decode a myriad of physical stimuli and are essential components of numerous mechanosensory processes. Central to their physiological role is the ability to change conformation in response to mechanical force. Here we discuss the evolutionary origin of Piezo in relation to other MS channels in addition to the force that gates Piezo channels. In particular, we discuss whether Piezo channels are inherently mechanosensitive in accordance with the force-from-lipid paradigm which has been firmly established for bacterial MS channels and two-pore domain K+ (K2P) channels. We also discuss the evidence supporting a reliance on or direct interaction with structural scaffold proteins of the cytoskeleton and extracellular matrix according to the force-from-filament principle. In doing so, we explain the false dichotomy that these distinctions represent. We also discuss the possible unifying models that shed light on channel mechanosensitivity at the molecular level.

Nanomechanical properties of MscL α helices: A steered molecular dynamics study.

Gating of mechanosensitive (MS) channels is driven by a hierarchical cascade of movements and deformations of transmembrane helices in response to bilayer tension. Determining the intrinsic mechanical properties of the individual transmembrane helices is therefore central to understanding the intricacies of the gating mechanism of MS channels. We used a constant-force steered molecular dynamics (SMD) approach to perform unidirectional pulling tests on all the helices of MscL in M. tuberculosis and E. coli homologs. Using this method, we could overcome the issues encountered with the commonly used constant-velocity SMD simulations, such as low mechanical stability of the helix during stretching and high dependency of the elastic properties on the pulling rate. We estimated Young's moduli of the α-helices of MscL to vary between 0.2 and 12.5 GPa with TM2 helix being the stiffest. We also studied the effect of water on the properties of the pore-lining TM1 helix. In the absence of water, this helix exhibited a much stiffer response. By monitoring the number of hydrogen bonds, it appears that water acts like a 'lubricant' (softener) during TM1 helix elongation. These data shed light on another physical aspect underlying hydrophobic gating of MS channels, in particular MscL.

Lipid-protein interactions: Lessons learned from stress.

Biological membranes are essential for normal function and regulation of cells, forming a physical barrier between extracellular and intracellular space and cellular compartments. These physical barriers are subject to mechanical stresses. As a consequence, nature has developed proteins that are able to transpose mechanical stimuli into meaningful intracellular signals. These proteins, termed Mechanosensitive (MS) proteins provide a variety of roles in response to these stimuli. In prokaryotes these proteins form transmembrane spanning channels that function as osmotically activated nanovalves to prevent cell lysis by hypoosmotic shock. In eukaryotes, the function of MS proteins is more diverse and includes physiological processes such as touch, pain and hearing. The transmembrane portion of these channels is influenced by the physical properties such as charge, shape, thickness and stiffness of the lipid bilayer surrounding it, as well as the bilayer pressure profile. In this review we provide an overview of the progress to date on advances in our understanding of the intimate biophysical and chemical interactions between the lipid bilayer and mechanosensitive membrane channels, focusing on current progress in both eukaryotic and prokaryotic systems. These advances are of importance due to the increasing evidence of the role the MS channels play in disease, such as xerocytosis, muscular dystrophy and cardiac hypertrophy. Moreover, insights gained from lipid-protein interactions of MS channels are likely relevant not only to this class of membrane proteins, but other bilayer embedded proteins as well. This article is part of a Special Issue entitled: Lipid-protein interactions.