Mechanobiology by the numbers: a close relationship between biology and physics.

Studies of mechanobiology lie at the interface of various scientific disciplines from biology to physics. Accordingly, quantification and mathematical modelling have been instrumental in fuelling the progress in this rapidly developing research field, assisting experimental work on many levels.

Physics meets biology: The joining of two forces to further our understanding of cellular function.

Some biological questions are tough to solve through standard molecular and cell biological methods and naturally lend themselves to investigation by physical approaches. Below, a group of formally trained physicists discuss, among other things, how they apply physics to address biological questions and how physical approaches complement conventional biological approaches.

On growth and force: mechanical forces in development.

The EMBO/EMBL Symposium 'Mechanical Forces in Development' was held in Heidelberg, Germany, on 3-6 July 2019. This interdisciplinary symposium brought together an impressive and diverse line-up of speakers seeking to address the origin and role of mechanical forces in development. Emphasising the importance of integrative approaches and theoretical simulations to obtain comprehensive mechanistic insights into complex morphogenetic processes, the meeting provided an ideal platform to discuss the concepts and methods of developmental mechanobiology in an era of fast technical and conceptual progress. Here, we summarise the concepts and findings discussed during the meeting, as well as the agenda it sets for the future of developmental mechanobiology.

Essay: Collections of Deformable Particles Present Exciting Challenges for Soft Matter and Biological Physics.

The field of soft matter physics has expanded rapidly over the past several decades, as physicists realize that a broad set of materials and systems are amenable to a physical understanding based on the interplay of entropy, elasticity, and geometry. The fields of biological physics and the physics of living systems have similarly emerged as bona fide independent areas of physics in part because tools from molecular and cell biology and optical physics allow scientists to make new quantitative measurements to test physical principles in living systems. This Essay will highlight two exciting future challenges I see at the intersection of these two fields: characterizing emergent behavior and harnessing actuation in highly deformable active objects. I will attempt to show how this topic is a natural extension of older and more recent discoveries and why I think it is likely to unfurl into a wide range of projects that can transform both fields. Progress in this area will enable new platforms for creating adaptive smart materials that can execute large-scale changes in shape in response to stimuli and improve our understanding of biological function, potentially allowing us to identify new targets for fighting disease. Part of a series of Essays which concisely present author visions for the future of their field.

Engineering the cellular mechanical microenvironment - from bulk mechanics to the nanoscale.

The field of mechanobiology studies how mechanical properties of the extracellular matrix (ECM), such as stiffness, and other mechanical stimuli regulate cell behaviour. Recent advancements in the field and the development of novel biomaterials and nanofabrication techniques have enabled researchers to recapitulate the mechanical properties of the microenvironment with an increasing degree of complexity on more biologically relevant dimensions and time scales. In this Review, we discuss different strategies to engineer substrates that mimic the mechanical properties of the ECM and outline how these substrates have been applied to gain further insight into the biomechanical interaction between the cell and its microenvironment.

Meeting Report - proteostasis in Ericeira.

It was a sunny Ericeira, in Portugal, that received the participants of the EMBO Workshop on Proteostasis, from 17 to 21 November 2017. Most participants gave talks or presented posters concerning their most recent research results, and lively scientific discussions occurred against the backdrop of the beautiful Atlantic Ocean.Proteostasis is the portmanteau of the words protein and homeostasis, and it refers to the biological mechanisms controlling the biogenesis, folding, trafficking and degradation of proteins in cells. An imbalance in proteostasis can lead to the accumulation of misfolded proteins or excessive protein degradation, and is associated with many human diseases. A wide variety of research approaches are used to identify the mechanisms that regulate proteostasis, typically involving different model organisms (yeast, invertebrates or mammalian systems) and different methodologies (genetics, biochemistry, biophysics, structural biology, cell biology and organismal biology). Around 140 researchers in the proteostasis field met in the Hotel Vila Galé, Ericeira, Portugal for the EMBO Workshop in Proteostasis, organized by Pedro Domingos (ITQB-NOVA, Oeiras, Portugal) and Colin Adrain (IGC, Oeiras, Portugal). In this report, we attempt to review and integrate the ideas that emerged at the workshop. Owing to space restrictions, we could not cover all talks or posters and we apologize to the colleagues whose presentations could not be discussed.

Developments in tandem ion mobility mass spectrometry.

Ion Mobility (IM) coupled to mass spectrometry (MS) is a useful tool for separating species of interest out of small quantities of heterogenous mixtures via a combination of m/z and molecular shape. While tandem MS instruments are common, instruments which employ tandem IM are less so with the first commercial IM-MS instrument capable of multiple IM selection rounds being released in 2019. Here we explore the history of tandem IM instruments, recent developments, the applications to biological systems and expected future directions.

The case for emulating insect brains using anatomical "wiring diagrams" equipped with biophysical models of neuronal activity.

Developing whole-brain emulation (WBE) technology would provide immense benefits across neuroscience, biomedicine, artificial intelligence, and robotics. At this time, constructing a simulated human brain lacks feasibility due to limited experimental data and limited computational resources. However, I suggest that progress toward this goal might be accelerated by working toward an intermediate objective, namely insect brain emulation (IBE). More specifically, this would entail creating biologically realistic simulations of entire insect nervous systems along with more approximate simulations of non-neuronal insect physiology to make "virtual insects." I argue that this could be realistically achievable within the next 20 years. I propose that developing emulations of insect brains will galvanize the global community of scientists, businesspeople, and policymakers toward pursuing the loftier goal of emulating the human brain. By demonstrating that WBE is possible via IBE, simulating mammalian brains and eventually the human brain may no longer be viewed as too radically ambitious to deserve substantial funding and resources. Furthermore, IBE will facilitate dramatic advances in cognitive neuroscience, artificial intelligence, and robotics through studies performed using virtual insects.

Neuroscience thinks big (and collaboratively).

Despite cash-strapped times for research, several ambitious collaborative neuroscience projects have attracted large amounts of funding and media attention. In Europe, the Human Brain Project aims to develop a large-scale computer simulation of the brain, whereas in the United States, the Brain Activity Map is working towards establishing a functional connectome of the entire brain, and the Allen Institute for Brain Science has embarked upon a 10-year project to understand the mouse visual cortex (the MindScope project). US President Barack Obama's announcement of the BRAIN Initiative (Brain Research through Advancing Innovative Neurotechnologies Initiative) in April 2013 highlights the political commitment to neuroscience and is expected to further foster interdisciplinary collaborations, accelerate the development of new technologies and thus fuel much needed medical advances. In this Viewpoint article, five prominent neuroscientists explain the aims of the projects and how they are addressing some of the questions (and criticisms) that have arisen.

Cell biology, biophysics, and mechanobiology: From the basics to Clinics.

Cell biology, biomechanics and biophysics are the key subjects that guide our understanding in diverse areas of tissue growth, development, remodeling and homeostasis. Novel discoveries such as molecular mechanism, and mechanobiological mechanism in cell biology, biomechanics and biophysics play essential roles in our understanding of the pathogenesis of various human diseases, as well as in designing the treatment of these diseases. In addition, studies in these areas will also facilitate early diagnostics of human diseases, such as cardiovascular diseases and cancer. In this special issue, we collected 10 original research articles and 1 review...

Achievements and challenges in structural bioinformatics and computational biophysics.

MOTIVATION: The field of structural bioinformatics and computational biophysics has undergone a revolution in the last 10 years. Developments that are captured annually through the 3DSIG meeting, upon which this article reflects. RESULTS: An increase in the accessible data, computational resources and methodology has resulted in an increase in the size and resolution of studied systems and the complexity of the questions amenable to research. Concomitantly, the parameterization and efficiency of the methods have markedly improved along with their cross-validation with other computational and experimental results. CONCLUSION: The field exhibits an ever-increasing integration with biochemistry, biophysics and other disciplines. In this article, we discuss recent achievements along with current challenges within the field.

Physics transforming the life sciences.

Biological physics is clearly becoming one of the leading sciences of the 21st century. This field involves the cross-fertilization of ideas and methods from biology and biochemistry on the one hand and the physics of complex and far from equilibrium systems on the other. Here I want to discuss how biological physics is a new area of physics and not simply applications of known physics to biological problems. I will focus in particular on the new advances in theoretical physics that are already flourishing today. They will become central pieces in the creation of this new frontier of science.

Physical Biology : challenges for our second decade.

It is quite an honor to be asked to become the third editor-in-chief of Physical Biology . I am following in the footsteps of Tim Newman, who served with energy and enthusiasm. Hopefully, the entire community fully appreciates his contributions to moving the field forward. Thank you, Tim! With the honor, however, goes a clear responsibility. Our journal has survived its birth pangs and emerged as a serious venue for publishing quality research papers using physical science to address the workings of living matter. With the support of scientists in this field and with the ongoing commitment of the IOP, we have successfully reached adolescence. Yet, there is clearly much room to grow and there are clear challenges in defining and maintaining our special niche in the publishing landscape. In this still-developing state, the journal very much mimics the state of the field of physical biology itself. Few scientists continue to question the relevance of physical science for the investigation of the living world. But, will our new perspective and the methods that come with it really lead to radically new principles of how life works? Or, will breakthroughs continue to come from experimental biology (perhaps aided by the traditional physicist-as-tool-builder paradigm), leaving us to put quantitative touches on established fundamentals? In thinking about these questions for the field and for the journal, I have tried to understand what is really unique about our joint endeavors. I have become convinced that living matter represents a new challenge to our physical-science based conceptual framework. Not only is it far from equilibrium, as has been generally recognized, but it violates our simple notions of the separability of constituents, their interactions and the resulting large-scale behavior. Unlike, say, atomic physicists who can do productive research while safely ignoring the latest developments in QCD (let alone particle physics at higher energies), we do not yet understand when the details of proteins and nucleic acids structure and function can be assumed constant when considering the cell. This problem is even more serious as we try to set higher sights and think of cells as constituents of tissue, organ and organism. Trying to understand higher-order biological systems is a bit like trying to play a board game where the pieces and rules are constantly changing, somehow in concert with what is happening at the scale of the game. Others will undoubtedly have their own view of what is really difficult and different about living systems. One of the roles of Physical Biology should therefore be to provide a needed forum to address some of these really difficult questions. Of course, most papers will operate with the safety-setting on, and will use established ideas in physics, either experimental or theoretical, to further our quantitative appreciation of living systems. These papers are without doubt an absolutely necessary part of the field, and we hope that our journal can serve as a home for the best of these. But, my real hope is that we can attract papers that really try to break new ground, that suggest ways in which the living world is not just an extremely messy example of the same phenomena that can be studied in non-biological contexts. Amazingly, this hope is actually shared by many leading biologists. In one of the most influential papers on cancer research in the past decades. Hanahan and Weinberg argue that 'one day, we imagine that cancer biology and treatment-at present, a patchwork quilt of cell biology, genetics, histopathology, biochemistry, immunology, and pharmacology-will become a science with a conceptual structure and logical coherence that rivals that of chemistry or physics.' We should take up the challenge, not just for cancer, and Physical Biology should help. Figuring out exactly how best to do this is now my responsibility, and I look forward to hearing from you and working with all of you, in order to make it happen.

Perspectives in biological physics: the nDDB project for a neutron Dynamics Data Bank for biological macromolecules.

Neutron spectroscopy provides experimental data on time-dependent trajectories, which can be directly compared to molecular dynamics simulations. Its importance in helping us to understand biological macromolecules at a molecular level is demonstrated by the results of a literature survey over the last two to three decades. Around 300 articles in refereed journals relate to neutron scattering studies of biological macromolecular dynamics, and the results of the survey are presented here. The scope of the publications ranges from the general physics of protein and solvent dynamics, to the biologically relevant dynamics-function relationships in live cells. As a result of the survey we are currently setting up a neutron Dynamics Data Bank (nDDB) with the aim to make the neutron data on biological systems widely available. This will benefit, in particular, the MD simulation community to validate and improve their force fields. The aim of the database is to expose and give easy access to a body of experimental data to the scientific community. The database will be populated with as much of the existing data as possible. In the future it will give value, as part of a bigger whole, to high throughput data, as well as more detailed studies. A range and volume of experimental data will be of interest in determining how quantitatively MD simulations can reproduce trends across a range of systems and to what extent such trends may depend on sample preparation and data reduction and analysis methods. In this context, we strongly encourage researchers in the field to deposit their data in the nDDB.

Tensile trabeculae--myth or reality?

Understanding of the functional role of the trabecular bone is very important for the analysis and computer-aided simulations of bone remodelling processes. The aspired wide clinical applications remain a remote future despite a great number of developed up-to-date approaches and theories and collected data on both material properties of the trabecular bone and its reaction to various stimuli. It is widely accepted that the mechanical loading plays the major role for the structure of the cancellous bone. The in vivo loading conditions of the cancellous bone are not known. Hence, for the computer-aided analysis and modelling of the trabecular bone specimens, simplified loading conditions are used. Also for the analysis of the cancellous bone as a part of a whole bone simplified loading conditions are assumed based on previous research without questioning its accuracy or relevance to the real in vivo conditions. In particular, the bending loading of the bone, which originates from the well-known observations made more than a century ago that have evolved in the trajectorial theory or "tensile trabeculae tradition", is often assumed to reflect the physiological loading conditions of bones. Some studies show that the bending or tensile-compressive orthogonal loading conditions for the cancellous bone may lead to plausible results. However, some other research works suggest that the presence of the tensile trabecular structures (particularly in the proximal femur) is doubtful and the bending loading conditions in bone should be treated with caution. Moreover, the loading conditions with compensated (or minimised) bending also produce results that correlate with the material distribution in the bone. The purpose of this review is to analyse some of the data and ideas available in the literature and to discuss the question of the major factors that define the shape and structure of the trabecular bone during the process of functional adaptation.

Physics, biology and the origin of life: the physicians' view.

Physicians have a great interest in discussions of life and its origin, including life's persistence through successive cycles of self-replication under extreme climatic and man-made trials and tribulations. We review here the fundamental processes that, contrary to human intuition, life may be seen heuristically as an ab initio, fundamental process at the interface between the complementary forces of gravitation and quantum mechanics. Analogies can predict applications of quantum mechanics to human physiology in addition to that already being applied, in particular to aspects of brain activity and pathology. This potential will also extend eventually to, for example, autoimmunity, genetic selection and aging. We present these thoughts in perspective against a background of changes in some physical fundamentals of science, from the earlier times of the natural philosophers of medicine to the technological medical gurus of today. Despite the enormous advances in medical science, including integration of technological changes that have led to the newer clinical applications of magnetic resonance imaging and PET scans and of computerized drug design, there is an intellectual vacuum as to how the physics of matter became translated to the biology of life. The essence and future of medicine continue to lie in cautious, systematic and ethically bound practice and scientific research based on fundamental physical laws accepted as true until proven false.