Physics

It is widely recognized that the shape of epithelial cells is determined by the tension generated by the actomyosin cortex and the adhesion of cells to the substrate and to each other. To account for these biological and structural contributions to cell shape, different physical models have been proposed. However, an experimental procedure that would allow a validation of a minimal physical model for the shape of epithelial cells in 3D has not yet been proposed. In this study, we cultured MDCK epithelial cells on substrates with a sinusoidal profile, allowing us to measure the shape of the cells on various positive and negative curvatures. We found that MDCK cells are thicker in the valleys than on the crests of sinusoidal substrates. The influence of curvature on the shape of epithelial cells could not be understood with a model using only differential apical, basal and lateral surface energies. However, the addition of an apical line tension was sufficient to quantitatively account for the experimental measurements. The model also accounts for the shape of MDCK cells that overexpress E-cadherin. On the other hand, when reducing myosin II activity with blebbistatin, we measured a saturation of the difference in cell thickness between valleys and crests, suggesting the need for a term limiting large cell deformations. Our results show that a minimal model that accounts for epithelial cell shape needs to include an apical line tension in addition to differential surface energies, highlighting the importance of structures that produce anisotropic tension in epithelial cells, such as the actin belt linking adherens junctions. In the future, our experimental procedure could be used to test a wider range of physical models for the shape of epithelia in curved environments, including, for example, continuous models.

I describe the non-equilibrium thermodynamics and the photochemical mechanisms which may have been involved in the dissipative structuring, proliferation and evolution of the fundamental molecules at the origin of life from simpler and more common precursor molecules under the impressed UVC photon flux of the Archean. Dissipative structuring of the fundamental molecules is evidenced by their strong and broad wavelength absorption bands and rapid radiationless dexcitation in this wavelength region. Proliferation arises from the auto- and cross-catalytic nature of the intermediate products. Evolution towards states of concentration profiles of generally increasing photon disspative efficacy arises since the system has numerous stationary states, due to the non-linearity of the photochemical and chemical reactions with diffusion, which can be reached by amplification of a molecular concentration fluctuation near a bifurcation. An example is given of photochemical dissipative abiogenisis of adenine from the precursors HCN and H 2 O within a fatty acid vesicle on a hot ocean surface, driven far from equilibrium by the impressed UVC light. The kinetic equations are resolved under different environmental conditions and the results analyzed within the framework of Classical Irreversible Thermodynamic theory.

In physics of living systems, a search for relationships of a few macroscopic variables that emerge from many microscopic elements is a central issue. We evolved gene regulatory networks so that the expression of target genes (partial system) is insensitive to environmental changes. Then, we found the expression levels of the remaining genes autonomously increase as a plastic response. Negative proportionality was observed between the average changes in target and remnant genes, reflecting reciprocity between the macroscopic robustness of homeostatic genes and plasticity of regulator genes. This reciprocity follows the lever principle, which was satisfied throughout the evolutionary course, imposing an evolutionary constraint.

Stimulated by ongoing discussions about the relevance of mechanical motion in the propagation of nerve signals capillary waves of water-based electrolytes in elastic tubular systems are considered as an essential ingredient. Their propagation velocities, controlled by the elastic properties and geometry of the neuron membrane as well as the density of the confined electrolyte, are shown to very well match observed nerve conduction velocities. As the capillary wave packets experience little damping and exhibit non-linear behavior they can propagate a soliton excitation. The orientation of water dipoles by the high electric fields up to about 10 million V/m in the about 1 nm thin layer adjacent to the elastic neuron membrane causes radial forces that modulate the diameter of the nerve cell with a change of the voltage bias across the cell membrane, caused, e. g., by local injection of ions. Acting like an electrically driven peristaltic pump the cell body thus can launch capillary waves into the axon which also transport neutral dipole current pulses modulated the varying voltage bias. At the synaptic end of the axon these dipole current pulses can cause voltage changes and initiate chemical signaling. In contrast to the traditional Hodgkin-Huxley model of nerve conduction the proposed mechanisms avoids charge currents and thus exhibits low dissipation. Specific features that could further influence and verify the proposed alternative mechanisms of nerve conduction are discussed.

Monte Carlo simulations are performed to study structure and dynamics of a protein CoVE in random media generated by a random distribution of barriers at concentration c with a coarse-grained model in its native (low temperature) and denatured (high temperature) phase. The stochastic dynamics of the protein is diffusive in denature phase at low c, it slows down on increasing c and stops moving beyond a threshold (cth = 0.10). In native phase, the protein moves extremely slow at low c but speeds up on further increasing c in a characteristic range (c = 0.10 - 0.20) before getting trapped at high c (cth = 0.30). The radius of gyration (Rg) of CoVE shows different non-monotonic dependence on c (increase followed by decay) in native and denature phase with a higher and sharper rate of change in farmer. Effective dimension (D) of CoVE is estimated from the scaling of structure factor: in denatured phase, D = 2 (a random coil conformation) at low c (= 0.01 - 0.10) with appearance of some globularization i.e. D ? 2.3, 2.5 at higher c (= 0.2, 0.3). Increasing c seems to reduce the globularity (D = 3) of CoVE in native phase.

Coupling hemodynamics with vessel wall growth and remodeling (G&R) is crucial for understanding pathology at distal vasculature to study progression of incurable vascular diseases, such as pulmonary arterial hypertension. The present study is the first modeling attempt that focuses on defining homeostatic baseline values in distal pulmonary vascular bed via, a so-called, homeostatic optimization. To define the vascular homeostasis and total hemodynamics in the vascular tree, we consider two time-scales: a cardiac cycle and a longer period of vascular adaptations. An iterative homeostatic optimization is performed at the slow-time scale and incorporates: an extended Murray's law, wall metabolic cost function, stress equilibrium, and hemodynamics. The pulmonary arterial network of small vessels is represented by a fractal bifurcating tree. The pulsatile blood flow is described by a Womersley's deformable wall analytical solution. A vessel wall mechanical response is described by the constrained mixture theory for an orthotropic membrane and then linearized around mean pressure. Wall material parameters are characterized by using available porcine pulmonary artery experiments and human data from literature. Illustrative examples for symmetric and asymmetric fractal trees are presented to provide homeostatic values in normal subjects. We also outline the key ideas for the derivation of a temporal multiscale formalism to justify the proposed one-way coupled system of governing equations and identify the inherent assumptions. The developed framework demonstrates a potential for advanced parametric studies and future G&R and hemodynamics modeling in pulmonary arterial hypertension.

This article presents a novel computational model to study the selective filtering of biological hydrogels due to the surface charge and size of diffusing particles. It is the first model that includes the random 3D fiber orientation and connectivity of the biopolymer network and that accounts for elastic deformations of the fibers by means of beam theory. As a key component of the model, novel formulations are proposed both for the electrostatic and repulsive steric interactions between a spherical particle and a beam. In addition to providing a thorough validation of the model, the presented computational studies yield new insights into the underlying mechanisms of hindered particle mobility, especially regarding the influence of the aforementioned aspects that are unique to this model. It is found that the precise distribution of fiber and thus charge agglomerations in the network have a crucial influence on the mobility of oppositely charged particles and gives rise to distinct motion patterns. Considering the high practical significance for instance with respect to targeted drug release or infection defense, the provided proof of concept motivates further advances of the model toward a truly predictive computational tool that allows a case- and patient-specific assessment for real (biological) systems.

The health threat from SARS-CoV-2 airborne infection has become a public emergency of international concern. During the ongoing coronavirus pandemic, people have been advised by the Centers for Disease Control and Prevention to maintain social distancing of at least 2 m to limit the risk of exposure to the coronavirus. Experimental data, however, show that infected aerosols and droplets trapped inside a turbulent puff cloud can travel up to 7 to 8 m. We propose a nuclear physics analogy-based modeling of the complex gas cloud and its payload of pathogen-virions. We show that the cloud stopping range is proportional to the product of the puff's diameter and its density. We use our puff model to determine the average density of the buoyant fluid in the turbulent cloud. A fit to the experimental data yields 1.8< ρ P / ρ air <4.0 , where ρ P and ρ air are the average density of the puff and the air. We demonstrate that temperature variation could cause an O(±8%) effect in the puff stopping range for extreme ambient cold or warmth. We also demonstrate that aerosols and droplets can remain suspended for hours in the air. Therefore, once the puff slows down sufficiently, and its coherence is lost, the eventual spreading of the infected aerosols becomes dependent on the ambient air currents and turbulence.

The question "What is life?" has been asked and studied by the researchers of various fields. Nevertheless, no global theory which unified various aspects of life has been proposed so far. Considering that the physical principle for the theory of birth should be the one known for the unanimated world, and that the life processes are irreversibly selective, we showed by a deductive inference that the maximum entropy production principle plays an essential role for the birth and the evolution of life in a fertile environment. In order to explain the survival strategy of life in a barren period of environment, we also proposed that life had simultaneously developed a reversible on and off switching mechanism of the chemical reactions by the dynamics of equilibrium thermodynamics. Thus, the birth and evolution of life have been achieved by the cooperation between the driving force due to the non-equilibrium thermodynamics and the protective force due to the equilibrium thermodynamics in the alternating environmental conditions.

The accumulation of potassium in the narrow space outside nerve cells is a classical subject of biophysics that has received much attention recently. It may be involved in potassium accumulation \textcolor{black}{including} spreading depression, perhaps migraine and some kinds of epilepsy, even (speculatively) learning. Quantitative analysis is likely to help evaluate the role of potassium clearance from the extracellular space after a train of action potentials. Clearance involves three structures that extend down the length of the nerve: glia, extracellular space, and axon and so need to be described as systems distributed in space in the tradition used for electrical potential in the `cable equations' of nerve since the work of Hodgkin in 1937. A three-compartment model is proposed here for the optic nerve and is used to study the accumulation of potassium and its clearance. The model allows the convection, diffusion, and electrical migration of water and ions. We depend on the data of Orkand et al to ensure the relevance of our model and align its parameters with the anatomy and properties of membranes, channels, and transporters: our model fits their experimental data quite well. The aligned model shows that glia has an important role in buffering potassium, as expected. The model shows that potassium is cleared mostly by convective flow through the syncytia of glia driven by osmotic pressure differences. A simplified model might be possible, but it must involve flow down the length of the optic nerve. It is easy for compartment models to neglect this flow. Our model can be used for structures quite different from the optic nerve that might have different distributions of channels and transporters in its three compartments. It can be generalized to include a fourth (distributed) compartment representing blood vessels to deal with the glymphatic flow into the circulatory system.