Frontiers in biophysics Big challenges in biophysics (2023)

• ¹D-BSSE, Catholic University of Leuven, Belgium

The field of biophysics has its roots at the turn of the 20th century. The term biophysics was first introduced by Karl Pearson in 1892, justifying it with the need to describe our perception of living organisms through the branch of science dealing with the application of the laws of inorganic or physical phenomena to complex organic forms [1]. The field tries to show how fundamentals of biology are actually special cases of general physics. Although the field did not make much progress at the time of its inception, it was immediately predicted to have a bright future. However, the formal establishment of biophysics as a separate scientific discipline is often credited to Max Delbrück and others who founded the first biophysics research groups in the 1940s. Since then, the field of biophysics has grown rapidly, growing exponentially over the last three decades (Figure 1), and the field now covers a wide range of disciplines and techniques, generating important contributions to our understanding of biological systems. But what exactly is biophysics? Where is the line between physics and biology? Is biophysics really physics or just the application of methods from physics to solve problems in biology? Today, biophysics is seen as a multidisciplinary field that combines physics, biology, chemistry and mathematics to study the physical and chemical processes that occur in living organisms. Biophysics undoubtedly springs from the desire to reconcile different visions of the same phenomenon. Faced with the same observation, physicists and biologists will approach the problem very differently, because their understanding of phenomena is based on different definitions. Relying on paradigms arising from historical discoveries in biology, biologists are losing touch with a more physical view that is based on deep theoretical knowledge, namely that there must be a physics of life, not just the physics of this system. While in biology the principle of the phenomenon will be explained by experimental discoveries, in physics the basic theory and experiment are more on the same basis. A set of interconnected theories and principles will determine what is possible and will be tested through a series of quantitative experiments. Biophysics aims to reconcile the physicist's desire to unify theoretical principles with the obvious variety of mechanisms of life perceived by biologists. The field covers many aspects of understanding biological phenomena at all levels, including but not limited to the structure and dynamics of individual molecules, the structure and mechanics of (macro)molecules, the study of physiological processes such as mechanotransduction or signaling in the cell and tissue level, understanding interactions with the immediate environment from a single cell to a whole organism, etc. In recent years, advances in biophysics are often inextricably linked. Technological developments have not only led to a better understanding of biological systems, but have also enabled scientists to develop new diagnostic techniques and advances in the treatment of certain diseases. The resolution of molecular structures, the characterization of molecular properties, and the understanding of cell behavior are, among others, huge challenges. for biophysicists. To access these properties, a plethora of (bio)physical techniques have been developed in recent decades with the main goal of further pushing the boundaries of characterization methods, whether in terms of resolution, dynamics, properties or analysis conditions. For example, biophysical approaches have helped to elucidate the structures of complex biological molecules such as proteins, nucleic acids and lipids. Techniques such as X-ray crystallography, NMR spectroscopy and cryo-electron microscopy allowed scientists to determine the three-dimensional structure of these molecules, which in turn led to an understanding of their function [2]. Biophysics has also enabled a better understanding of the physical and chemical mechanisms underlying biological processes such as enzyme catalysis [3], protein folding [4] and molecular recognition [5]. For example, studies of the mechanical properties of proteins and DNA have shed light on their role in cellular processes such as DNA replication and protein synthesis [6,7]. This progress was possible thanks to the development of new methods that allow manipulating individual molecules, enabling direct measurement of the forces generating biochemical reactions, and even exerting external forces to change the course of these reactions [8]. contributed to a better understanding of the properties and functions of biological membranes and their molecular machinery, which are essential for cell survival. More than two decades ago, a new aspect of cell membrane organization was introduced, based on the dynamic aggregation of sphingolipids and cholesterol to form rafts moving in the fluid bilayer [9]. This concept is based on the use of multiple biophysical techniques that independently demonstrate the association of sphingolipids and cholesterol, including immuno-etching electron microscopy, fluorescence microscopy, differential scanning calorimetry, spin-tagged electron resonance or nuclear magnetic resonance spectroscopy. In addition to rafts, hot lines of evidence have been reported for larger and more stable domains, whether or not enriched with cholesterol and sphingolipids, in artificial membranes, fixed cells, and more recently in living cells [10][11][12]. Lipid asymmetry refers to the differential distribution of lipids between the inner and outer layers of the membrane and results in different biophysical properties between the layers. The maintenance of this lipid asymmetry between the layers, provided by specific lipid transporters and flippases, is associated with high energy costs, but is essential for some cellular functions, such as cell protection or signal transduction [13]. The lateral organization of lipids into rafts or microdomains has a significant impact on the functional states of membrane proteins [14]. For example, the asymmetric distribution of phosphatidylserine in the inner layer of the cell membrane is recognized by some proteins involved in the elimination of apoptotic cells, and some lipids such as PIP2 are known to regulate the conformational dynamics of certain G protein-coupled receptors (GPCRs). Techniques such as fluorescence microscopy/spectroscopy and electron microscopy were used to study membrane structure and dynamics, membrane protein structure and dynamics, and the transport of ions and molecules across membranes. In addition to in vitro and in vivo experiments, the in silico approach appears to be a highly complementary approach, providing detailed insights into molecular interactions that cannot be directly observed by experimental methods. For example, simulations are very helpful in studying how a protein interacts with a drug molecule [15] or how water molecules move around a protein [16]. In addition, simulations can help understand the effects of mutations and predict how these changes may affect protein function [17]. By applying the principles of physics to biological systems, biophysics has provided tools and techniques to detect and measure biological molecules, cells and tissues with high sensitivity and specificity. Development of various imaging techniques to visualize biological structures and processes. For example, X-rays, magnetic resonance imaging, positron emission tomography and ultrasound are based on the physical principles of how waves work and how they interact with biological tissues. These techniques are widely used in clinical diagnosis and disease monitoring. Biophysics has also contributed to the development of biosensors that can detect biological molecules such as proteins, DNA and RNA with high sensitivity and specificity. Biosensors rely on physical phenomena such as surface plasmon resonance, fluorescence and electrochemistry. They are used for early diagnosis and disease monitoring, as well as in research applications. The future of biophysics © Thinkstock Biological phenomena cover a wide range of temporal and spatial scales, ranging from femtosecond molecular movements to processes taking place over minutes, hours and even days, such as protein folding, cycle regulation, cell and biodistribution. At the same time, biological systems of interest can range from small molecules to complexes of multiple proteins, cells, tissues, and entire populations. Therefore, understanding the formation of collective phenomena as a result of interactions and conformational changes of molecular species at the smallest scale is a major challenge. To address this, one of the biggest challenges facing biophysics in the future is not only integrating the different technologies and approaches used to study biological systems, but also developing new tools and techniques to study biological systems at different levels. organization. from the molecular level to the organism. This will require the development of new interdisciplinary collaborations and a better understanding of the underlying principles of biological systems. To meet this challenge, they will also need to use their experience in modeling complex systems based on mathematical and computational tools. For example, scientists will need to develop new approaches to integrate information obtained from molecular imaging, computational simulations and experimental measurements to gain a comprehensive understanding of biological systems. Another challenge facing the field of biophysics in the future is to apply the knowledge gained from biophysical research to improve human health. This will require the development of new therapeutic strategies based on an understanding of the physical and chemical processes underlying the onset of disease and how these processes can be disrupted to restore healthy conditions. In summary, biophysics is a rapidly evolving field that plays a key role in our understanding of biological systems. The development of new technologies and approaches, as well as the integration of different disciplines, will be essential to meet the great challenges biophysics will face in the future. Through continued research and collaboration, biophysicists will continue to make important contributions to our understanding of living organisms and the development of new treatments for disease.
In summary, the area of ​​biophysics involves the study of the physical principles underlying all processes in living systems, and is also related to other disciplines such as mathematics and chemistry. Frontiers in Biophysics will publish high-quality original articles as well as review articles that use a physics-based approach or methods to better understand biological systems and their functions. This journal is part of the Frontiers editorial structure, which offers biophysicists a new opportunity to publish their papers in an open access journal through a transparent peer review process.

Keywords:Biophysics, X-ray crystallography, NMR spectroscopy, electron cryomicroscopy (cryo-EM), biophysical techniques

Received:2 houses 2023;Adopted:18 maja 2023 r.

Copyright:© 2023 Alsteens. This is an open access article distributed under termsLicencja Creative Commons Attribution (CC BY). Use, distribution or reproduction in other forums is permitted provided the name of the original author(s) or licensor is credited and the original publication in this journal is cited in accordance with accepted scientific practice. Any use, distribution or reproduction not in accordance with these terms is not permitted.

* Correspondence:dr. David Alsteens, Universidad Católica de Louvain, D-BSSE, Louvain-la-Neuve, Belgium