Biophysics reviews最新文献

The association and dissociation of proteins and ligands are crucial in biophysics for potential drug development [Baron and McCammon, Annu. Rev. Phys. Chem. 64, 151-175 (2013)]. However, identifying and characterizing the reaction pathways for these rare events has been a long-standing challenge. Molecular dynamics (MD) simulations are limited in exploring biophysical processes on experimental timescales, so ligand transport processes through complex transient tunnels formed by proteins during dynamics are often simulated using enhanced sampling MD [Rydzewski and Nowak, Phys. Life Rev. 22-23, 58-74 (2017)]. Erroneously identified ligand binding pathways can affect thermodynamic and kinetic characteristics calculated from MD trajectories. A system that has the potential to be a therapeutic target for neurodegenerative diseases is prolyl oligopeptidase (PREP). This is due to its involvement in promoting protein aggregation and disrupting cellular function through affecting protein-protein interactions (PPI). The recent discovery of a new type of PREP inhibitor that targets PPI raises important questions about the diversity of ligand binding pathways in PREP and their impact on protein dynamics [Pätsi et al., J. Med. Chem. 67, 5421-5436 (2024); Kilpeläinen et al., J. Med. Chem. 66, 7475-7496 (2023); and Walczewska-Szewc et al., Phys. Chem. Chem. Phys. 24, 4366-4373 (2022)]. In this article, using results from enhanced sampling MD, we visually present how the binding process in PREP depends on subtle changes in inhibitors, which could be crucial in treating neurodegenerative disorders.

Protein/peptide amyloid fibril formation is associated with various neurodegenerative diseases and, hence, has been the subject of extensive studies. From a structure-evolution point of view, we now know a great deal about the initial and final states of this process; however, we know very little about its intermediate states. Herein, we employ liquid-phase transmission electron microscopy to directly visualize the formation of one of the intermediates formed during the aggregation process of an amyloid-forming peptide. As shown in figure, we find that Aβ42, the amyloid formation of which has been linked to the development of Alzheimer's disease, can populate a ring-shaped intermediate structure with a diameter of tens of nanometers; additionally, the air-liquid interface can "catalyze" the formation of amyloid fibrils.

Hairs are fundamental structures for mammals, serving crucial functions such as thermal insulation and hydrophobicity. In domestic animals, hair is also a valuable source of high-performance fibers for the textile industry, which has led to intensive study. However, there is limited comparative knowledge about the physical properties of hair across different wild mammalian species. In our lab, we are investigating the physical properties of hairs from a diverse range of wild mammalian species, laying the groundwork for an in-depth comparative study. These physical properties can be linked to the internal structures of the hairs. Using polarized light microscopy, we can visualize the internal structure of hairs, which are composed of a hollow channel (medulla) surrounded by a cortex and a keratin cuticle(1). By examining the brown hairs of three distinct mammals-the Patagonian mara, the brown bear, and the Amur tiger-we observe striking differences in their internal structures. We speculate that these structural differences correspond to varying physical properties, which we are currently investigating.

Living cells can perform incredible tasks that man-made micro/nano-sized robots have not yet been able to accomplish. One example is that white blood cells can sense and move to the site of pathogen attack within minutes. The robustness and precision of cellular functions have been perfected through billions of years of evolution. In this context, we ask the question whether cells follow a set of physical principles to sense, adapt, and migrate. Microfluidics has emerged as an enabling technology for recreating well-defined cellular environment for cell migration studies, and its ability to follow single cell dynamics allows for the results to be amenable for theoretical modeling. In this review, we focus on the development of microfluidic platforms for recreating cellular biophysical (e.g., mechanical stress) and biochemical (e.g., nutrients and cytokines) environments for cell migration studies in 3D. We summarize the basic principles that cells (including bacteria, algal, and mammalian cells) use to respond to chemical gradients learned from microfluidic systems. We also discuss about novel biological insights gained from studies of cell migration under biophysical cues and the need for further quantitative studies of cell function under well-controlled biophysical environments in the future.

3D bioprinting techniques enable the precise deposition of living cells, biomaterials, and biomolecules, emerging as a promising approach for engineering functional tissues and organs. Meanwhile, recent advances in 3D bioprinting enable researchers to build in vitro models with finely controlled and complex micro-architecture for drug screening and disease modeling. Recently, artificial intelligence (AI) has been applied to different stages of 3D bioprinting, including medical image reconstruction, bioink selection, and printing process, with both classical AI and machine learning approaches. The ability of AI to handle complex datasets, make complex computations, learn from past experiences, and optimize processes dynamically makes it an invaluable tool in advancing 3D bioprinting. The review highlights the current integration of AI in 3D bioprinting and discusses future approaches to harness the synergistic capabilities of 3D bioprinting and AI for developing personalized tissues and organs.

Polymeric fibrin provides the structural and mechanical stability of a blood clot. Fibrin fibers are rod-like and create a network mesh that holds blood cells. When a clot has performed its physiological function in wound healing and preventing excessive blood loss, it must be resolved by the enzymatic degradation of fibrin, otherwise known as fibrinolysis. If a blood clot forms when or where it is not needed, as occurs in ischemic strokes and myocardial infarctions, the blood clot (thrombus) can obstruct blood flow to downstream organs. Obstructive thrombi must be degraded or removed to prevent further complications. If a clot is not degraded on its own, lytic agents (i.e., tissue plasminogen activator, tPA) are given exogenously to induce fibrinolysis. Here, we fluorescently labeled both fibrin and tPA to visualize degradation at the edge of the clot. The fibers with bound tPA were looped or coiled while the fibers farther into the clot remain straight and stable displaying the diffusion of tPA and depth of lysis. This image provides (1) a new method to monitor fibrinolysis with a commercially available chamber with convenient inlets and (2) the visualization of tPA-bound fibrin and the behavior of fibers during degradation. Future work could utilize this technique to study tPA molecule and fibrin interactions, lysis front degradation, and fibrin fiber linearity to understand the mechanisms of intermolecular dynamics dependent on network structure. An enhanced insight into this process can aid in the development of optimized therapeutics to target stubborn clots.

Originally developed more than 20 years ago, engineered heart tissue (EHT) has become an important tool in cardiovascular research for applications such as disease modeling and drug screening. Innovations in biomaterials, stem cell biology, and bioengineering, among other fields, have enabled EHT technologies to recapitulate many aspects of cardiac physiology and pathophysiology. While initial EHT designs were inspired by the isolated-trabecula culture system, current designs encompass a variety of formats, each of which have unique strengths and limitations. In this review, we describe the most common EHT formats, and then systematically evaluate each aspect of their design, emphasizing the rational selection of components for each application.

Macrophages play pivotal roles in the immune response, participating in both inflammatory and pro-healing processes. Like other cells, macrophages continually survey their microenvironment through mechanosensing, adapting their intracellular organization in response to mechanical signals. In this study, we elucidate how macrophages perceive the topographical cues of wrinkled surfaces through actin-based structures, which align with the main pattern direction, thus modulating cell cytoskeletal dynamics. Given that such alterations may regulate mechanosensitive gene expression programs, exploring cellular responses to biomaterial design becomes crucial for developing biomaterials that mitigate adverse reactions.

Cell migration is a fundamental process for life and is highly dependent on the dynamical and mechanical properties of the cytoskeleton. Intensive physical and biochemical crosstalk among actin, microtubules, and intermediate filaments ensures their coordination to facilitate and enable migration. In this review, we discuss the different mechanical aspects that govern cell migration and provide, for each mechanical aspect, a novel perspective by juxtaposing two complementary approaches to the biophysical study of cytoskeletal crosstalk: live-cell studies (often referred to as top-down studies) and cell-free studies (often referred to as bottom-up studies). We summarize the main findings from both experimental approaches, and we provide our perspective on bridging the two perspectives to address the open questions of how cytoskeletal crosstalk governs cell migration and makes cells move.

The magnetic field produced by the heart's electrical activity is called the magnetocardiogram (MCG). The first 20 years of MCG research established most of the concepts, instrumentation, and computational algorithms in the field. Additional insights into fundamental mechanisms of biomagnetism were gained by studying isolated hearts or even isolated pieces of cardiac tissue. Much effort has gone into calculating the MCG using computer models, including solving the inverse problem of deducing the bioelectric sources from biomagnetic measurements. Recently, most magnetocardiographic research has focused on clinical applications, driven in part by new technologies to measure weak biomagnetic fields.