Biophysics reviews最新文献

Cardiac arrhythmias are an important cause of sudden cardiac death-a devastating manifestation of many underlying causes, such as heart failure and ischemic heart disease leading to ventricular tachyarrhythmias and ventricular fibrillation, and atrial fibrillation causing cerebral embolism. Cardiac electrical propagation is a main factor in the initiation and maintenance of cardiac arrhythmias. In the heart, gap junctions are the basic unit at the cellular level that host intercellular low-resistance channels for the diffusion of ions and small regulatory molecules. The dual voltage clamp technique enabled the direct measurement of electrical conductance between cells and recording of single gap junction channel openings. The rapid turnover of gap junction channels at the intercalated disk implicates a highly dynamic process of trafficking and internalization of gap junction connexons. Recently, non-canonical roles of gap junction proteins have been discovered in mitochondria function, cytoskeletal organization, trafficking, and cardiac rescue. At the tissue level, we explain the concepts of linear propagation and safety factor based on the model of linear cellular structure. Working myocardium is adequately represented as a discontinuous cellular network characterized by cellular anisotropy and connective tissue heterogeneity. Electrical propagation in discontinuous cellular networks reflects an interplay of three main factors: cell-to-cell electrical coupling, flow of electrical charge through the ion channels, and the microscopic tissue structure. This review provides a state-of-the-art update of the cardiac gap junction channels and their role in cardiac electrical impulse propagation and highlights a combined approach of genetics, cell biology, and physics in modern cardiac electrophysiology.

A decade ago, environmental issues, such as air pollution and the contamination of the oceans with microplastic, were prominently communicated in the media. However, these days, political topics, as well as the ongoing COVID-19 pandemic, have clearly taken over. In spite of this shift in focus regarding media representation, researchers have made progress in evaluating the possible health risks associated with particulate contaminations present in water and air. In this review article, we summarize recent efforts that establish a clear link between the increasing occurrence of certain pathological conditions and the exposure of humans (or animals) to airborne or waterborne particulate matter. First, we give an overview of the physiological functions mucus has to fulfill in humans and animals, and we discuss different sources of particulate matter. We then highlight parameters that govern particle toxicity and summarize our current knowledge of how an exposure to particulate matter can be related to dysfunctions of mucosal systems. Last, we outline how biophysical tools and methods can help researchers to obtain a better understanding of how particulate matter may affect human health. As we discuss here, recent research has made it quite clear that the structure and functions of those mucosal systems are sensitive toward particulate contaminations. Yet, our mechanistic understanding of how (and which) nano- and microparticles can compromise human health via interacting with mucosal barriers is far from complete.

In past decades, the exploitation of silver nanoparticles in novel antibacterial and detection devices has risen to prominence, owing to the well-known specific interaction of silver with bacteria. The vast majority of the investigations focus on the investigation over the mechanism of action underpinning bacterial eradication, while few efforts have been devoted to the study of the modification of silver optical properties upon interaction with bacteria. Specifically, given the characteristic localized surface plasmon resonance of silver nanostructures, which is sensitive to changes in the charge carrier density or in the dielectric environment, these systems can offer a handle in the detection of bacteria pathogens. In this review, we present the state of art of the research activity on the interaction of silver nanoparticles with bacteria, with strong emphasis on the modification of their optical properties. This may indeed lead to easy color reading of bacterial tests and pave the way to the development of nanotechnologic silver-based bacterial detection systems and drug-screening platforms.

Cell-driven plastic remodeling of the extracellular matrix (ECM) is a key regulator driving cell invasion and organoid morphogenesis in 3D. While, mostly, the linear properties are reported, the nonlinear and plastic property of the used matrix is required for these processes to occur. Here, we report on the nonlinear and plastic mechanical properties of networks derived from collagen I, Matrigel, and related hybrid gels and link their mechanical response to the underlying collagen structure. We reveal the predominantly linear behavior of Matrigel over a wide range of strains and contrast this to the highly nonlinear and plastic response of collagen upon mechanical load. We show that the mechanical nonlinear response of collagen can be gradually diminished by enriching the network stepwise with Matrigel. This tunability results from the suppression of collagen polymerization in the presence of Matrigel, resulting in a collagen network structure with significant smaller mesh size and consequent contribution to the mechanical response. Thus, the nonlinear plastic properties and structure of the ECM is not simply the addition of two independent network types but depends on the exact polymerization conditions. The understanding of this interplay is key toward an understanding of the dependencies of cellular interactions with their ECM and sheds light on the nonlinear cell-ECM interaction during organogenesis.

Cellular matter can be spatially and temporally organized into membraneless biomolecular condensates. The current thinking is that these condensates form and dissolve via phase transitions driven by one or more condensate-specific multivalent macromolecules known as scaffolds. Cells likely regulate condensate formation and dissolution by exerting control over the concentrations of regulatory molecules, which we refer to as ligands. Wyman and Gill introduced the framework of polyphasic linkage to explain how ligands can exert thermodynamic control over phase transitions. This review focuses on describing the concepts of polyphasic linkage and the relevance of such a mechanism for controlling condensate formation and dissolution. We describe how ligand-mediated control over scaffold phase behavior can be quantified experimentally. Further, we build on recent studies to highlight features of ligands that make them suppressors vs drivers of phase separation. Finally, we highlight areas where advances are needed to further understand ligand-mediated control of condensates in complex cellular environments. These advances include understanding the effects of networks of ligands on condensate behavior and how ligands modulate phase transitions controlled by different combinations of homotypic and heterotypic interactions among scaffold macromolecules. Insights gained from the application of polyphasic linkage concepts should be useful for designing novel pharmaceutical ligands to regulate condensates.

Almost all cases of cervical cancer are caused by the human papilloma virus (HPV). Detection of pre-cancerous cervical changes provides a window of opportunity for cure of an otherwise lethal disease when metastatic. With a greater understanding of the biology and natural course of high-risk HPV infections, screening methods have shifted beyond subjective Pap smears toward more sophisticated and objective tactics. This has led to a substantial growth in the breadth and depth of HPV-based cervical cancer screening tests, especially in developed countries without constrained resources. Many low- and middle-income countries (LMICs) have less access to advanced laboratories and healthcare resources, so new point-of-care (POC) technologies have been developed to provide test results in real time, improve the efficiency of techniques, and increase screening adoption. In this Review, we will discuss how novel decentralized screening technologies and computational strategies improve upon traditional methods and how their realized promise could further democratize cervical cancer screening and promote greater disease prevention.

Many processes in chemistry and biology involve interactions of a ligand with its molecular target. Interest in the mechanism governing such interactions has dominated theoretical and experimental analysis for over a century. The interpretation of molecular recognition has evolved from a simple rigid body association of the ligand with its target to appreciation of the key role played by conformational transitions. Two conceptually distinct descriptions have had a profound impact on our understanding of mechanisms of ligand binding. The first description, referred to as induced fit, assumes that conformational changes follow the initial binding step to optimize the complex between the ligand and its target. The second description, referred to as conformational selection, assumes that the free target exists in multiple conformations in equilibrium and that the ligand selects the optimal one for binding. Both descriptions can be merged into more complex reaction schemes that better describe the functional repertoire of macromolecular systems. This review deals with basic mechanisms of ligand binding, with special emphasis on induced fit, conformational selection, and their mathematical foundations to provide rigorous context for the analysis and interpretation of experimental data. We show that conformational selection is a surprisingly versatile mechanism that includes induced fit as a mathematical special case and even captures kinetic properties of more complex reaction schemes. These features make conformational selection a dominant mechanism of molecular recognition in biology, consistent with the rich conformational landscape accessible to biological macromolecules being unraveled by structural biology.