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.

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.

Imaging methods in mechanosensing: a historical perspective and visions for the future.

Over the past three decades, as mechanobiology has become a distinct area of study, researchers have developed novel imaging tools to discover the pathways of biomechanical signaling. Early work with substrate engineering and particle tracking demonstrated the importance of cell-extracellular matrix interactions on the cell cycle as well as the mechanical flux of the intracellular environment. Most recently, tension sensor approaches allowed directly measuring tension in cell-cell and cell-substrate interactions. We retrospectively analyze how these various optical techniques progressed the field and suggest our vision forward for a unified theory of cell mechanics, mapping cellular mechanosensing, and novel biomedical applications for mechanobiology.

Helical growth during the phototropic response, avoidance response, and in stiff mutants of Phycomyces blakesleeanus.

The sporangiophores of Phycomyces blakesleeanus have been used as a model system to study sensory transduction, helical growth, and to establish global biophysical equations for expansive growth of walled cells. More recently, local statistical biophysical models of the cell wall are being constructed to better understand the molecular underpinnings of helical growth and its behavior during the many growth responses of the sporangiophores to sensory stimuli. Previous experimental and theoretical findings guide the development of these local models. Future development requires an investigation of explicit and implicit assumptions made in the prior research. Here, experiments are conducted to test three assumptions made in prior research, that (a) elongation rate, (b) rotation rate, and (c) helical growth steepness, R, of the sporangiophore remain constant during the phototropic response (bending toward unilateral light) and the avoidance response (bending away from solid barriers). The experimental results reveal that all three assumptions are incorrect for the phototropic response and probably incorrect for the avoidance response but the results are less conclusive. Generally, the experimental results indicate that the elongation and rotation rates increase during these responses, as does R, indicating that the helical growth steepness become flatter. The implications of these findings on prior research, the "fibril reorientation and slippage" hypothesis, global biophysical equations, and local statistical biophysical models are 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.

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.

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.

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.

Can research align with service? Lessons learned from the Big Experiment and National Biomechanics Day.

Public engagement is an important role for the university academic, but is often neglected due to perceived lack of time and prioritized commitments in research and teaching. Yet, public engagement events offer an untapped opportunity for researchers to collect data from members of the general public who arrive on site at university labs. These engagement events could allow for data collection as part of didactic and demonstrative outreach events to be used in research and science. In this proof of concept study, a collaborative group of international researchers investigated the feasibility of embedding research quality assessment into events surrounding National Biomechanics Day. The Big Experiment collected data on 501 secondary school students (age range: 13 to 18 years) across 9 university sites within a 24-hour period. Data included maximal vertical jump height and self-reported physical activity levels. Vertical jump height was positively correlated to participant height, but not age or body mass. Very physically active students had significantly higher vertical jump heights than individuals who reported being somewhat or not physically active. This feasibility project demonstrates that with substantial preparation and a simple research design, focused research questions can be incorporated into educational outreach initiatives and ultimately provide a rich data source.

[Bone mechanobiology, an emerging field: a review]. / La mécanobiologie osseuse, un domaine émergeant : revue de littérature.

INTRODUCTION: Mechanobiology, at the interface between biology and biophysics, studies the impact of mechanical forces on tissues, cells and biomolecules. The application of orthodontic forces, followed by induced tooth displacement, is a striking example of its clinical application. OBJECTIVE: The purpose of this article was to compile a review of the literature on the subject of mechanobiology; from its detection at bone level to the presentation of stimulated intracellular pathways. MATERIALS AND METHODS: The literature search was conducted on the Pubmed database in April 2018, with associations of the terms "mechanobiology", "orthodontics", "cell culture", "physiopathology". RESULTS: Three major areas of research were selected: highlighting of the phenomenon and its application in the field of bone biology; the cellular effectors of mechanobiology and its clinical applications. The use of mechanobiology in dentofacial orthopedics opens up a new field of reflection for clinicians regarding future advances in orthodontics.

The future of quantum biology.

Biological systems are dynamical, constantly exchanging energy and matter with the environment in order to maintain the non-equilibrium state synonymous with living. Developments in observational techniques have allowed us to study biological dynamics on increasingly small scales. Such studies have revealed evidence of quantum mechanical effects, which cannot be accounted for by classical physics, in a range of biological processes. Quantum biology is the study of such processes, and here we provide an outline of the current state of the field, as well as insights into future directions.

Quantum theory of mass potentials.

Probabilistic formalism of quantum mechanics is used to quantitatively link the global scale mass potential with the underlying electrical activity of excitable cells. Previous approaches implemented methods of classical physics to reconstruct the mass potential in terms of explicit physical models of participating cells and the volume conductor. However, the multiplicity of cellular processes with extremely intricate mixtures of deterministic and random factors prevents the creation of consistent biophysical parameter sets. To avoid the uncertainty inherent in physical attributes of cell ensembles, we undertake here a radical departure from deterministic equations of classical physics, instead applying the probabilistic reasoning of quantum mechanics. Crucial steps include: (1) the relocation of the elementary bioelectric sources from a cellular to a molecular level; (2) the creation of microscale particle models in terms of a non-homogenous birth-and-death process. To link the microscale processes with macroscale potentials, time-frequency analysis was applied for estimation of the empirical characteristic functions for component waveforms of electroencephalogram (EEG), eye-blink electromyogram (EMG), and electrocardiogram (ECG). We describe universal models for the amplitude spectra and phase functions of functional components of mass potentials. The corresponding time domain relationships disclose the dynamics of mass potential components as limit distribution functions produced by specific microscale transients. The probabilistic laws governing the microscale machinery, founded on an empirical basis, are presented. Computer simulations of particle populations with time dependent transition probabilities reveal that hidden deterministic chaos underlies development of the components of mass potentials. We label this kind of behaviour "transient deterministic chaos".

Targeting Biophysical Cues: a Niche Approach to Study, Diagnose, and Treat Cancer.

Probing the biophysical properties of the tumor niche offers a new perspective in cancer mechanobiology, and supports the development of next-generation diagnostics and therapeutics for cancer, in particular for metastasis.

Transport Barriers and Oncophysics in Cancer Treatment.

Transport processes in cancer are the focus of transport oncophysics (TOP). In the TOP approach, the sequential negotiation of transport barriers is critical to both drug delivery and metastasis development. New and creative therapeutic opportunities are currently emerging, stimulated by the study of cancer hallmarks with the TOP approach.

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.

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.