The research themes covered by the AQV network can be organized into several broad questions, on which biology and physics take complementary angles, as outlined below.

1. Dynamics of molecular assemblies (active matter)

Biomolecular complexes are far-from-equilibrium systems. Thus, our understanding of their dynamics (molecular selectivity, energy yield, force-affinity relationships) can directly benefit from new tools of non-equilibrium statistical physics (fluctuation theorems, large deviation functions, etc.). This opens new perspectives for the design of biomimetic systems and in synthetic biology: our ability to better understand the interactions between molecules or biological complexes (DNA, DNA/proteins) allows us to build actual molecular computers and to reconstruct elementary motifs (such as feedback loops) that are present in intracellular signaling pathways. In cell biology as well, the dynamics of the cytoskeleton (actin, microtubules, and intermediate filaments) and its interactions with other cell organelles (nucleus, membranes) are crucial for force transmission within and between cells (see theme 2). Another emergent example in cell biology is the formation of self-organized protein liquid droplets, which emerge through a phase separation mechanism involving low affinity and multivalence. These droplets form in the cytoplasm in response to stress (stress granules), and they are at the origin of membrane-less organelles (nucleoli, p-granules, centrosomes, RNA-bodies). More recently, such liquid droplets have been observed in the nucleus, where they regulate major biological functions (chromatin compartments, transcription hubs). Recent work in this field is revisiting and extending discoveries made previously on liquid-liquid phase transitions in the field of soft matter.

2. Cell and tissue mechanics (forces and tensions)

Understanding the phenomena of mechanotransduction, by which forces are converted into biochemical activity, and the transmission of forces across scales, is a major challenge in contemporary cell biology, for which physical approaches are indispensable. Following the development of approaches that make it possible to measure and perturb on the scale of a single cell the parameters that govern its mechanical properties, its shape, its adhesion, and its migratory potential, the next steps will be to couple dynamic measurements of these parameters with selective mechanical measurements at the molecular scale in situ, and with dynamic perturbations of intracellular biochemical activities. The contribution of optogenetics, combined with quantitative microscopy of genetically encoded biosensors in model environments that mimick the mechanical parameters observed in vivo, will be decisive. On a larger scale, tissue mechanics is essential to understand morphogenetic processes in developmental biology. Many developmental biologists now collaborate with physicists to approach morphogenesis from a mechanical perspective. The development of experimental and theoretical tools to measure and perturb stresses in situ in living organisms, and to describe the mechanics of these peculiar materials that exhibit feedbacks between stress and growth will also be crucial. From a theoretical standpoint, biological tissues can be viewed as disordered systems, and their study can draw on the tools of statistical physics, while opening new questions owing to their specific nature (as active, mechano-sensitive systems).

3. Regulation, signaling, networks, systems (biological information)

Cells must simultaneously respond to external stimuli, orchestrate different biological functions, maintain an adequate homeostatic state to function, and make important decisions about their fate. To do so, they rely on signaling networks with numerous feedback loops, whose dynamics can be complex and counterintuitive. Similarly, the different cells of an organism communicate with each other by contact or at a distance, and coordinate via a multitude of biochemical, mechanical, and electrical pathways. Biological systems thus create, transmit, and process information in the form of different signals, making use of true algorithms which, to be robust and optimal, must take into account the nature of these signals and their limitations. To approach these questions, we can leverage dynamical systems theory, to understand how generic dynamics (bistability, oscillations, critical points, etc.) are mobilized, as well as statistical physics, to quantify how a robust and multiplexed encoding is possible (mutual information, molecular selectivity, etc.). Physicists, who have developed a theory of information based on statistical physics, should thus join forces with biologists to address the meaning of information in biology, from the molecular to the systemic scale, in order to better understand the principles of cellular dynamics. Moreover, the accumulation of massive data in biology calls for new tools to extract information from raw data. These emergent tools draw on concepts from physics (inference, deep learning) and require the involvement of biophysicists as well as bioinformaticians.

4. Collective phenomena (multiscale interactions, complexity, and self-organization)

In many multicellular systems, emergent properties at the macroscopic scale arise from interactions on the cellular scale, which thus stands as the relevant scale to understand collective dynamics. The physics of complex systems offers many tools to describe such biological objects. Indeed, a growing number of collective processes in biology have been successfully described by interdisciplinary approaches, among which :

• the self-organization of spatial structures in the development of multicellular organisms (via molecular or mechanical signals; studied in vivo or reconstructed in vitro), the synchronization of genetic oscillations (somitogenesis, circadian rhythms)
• evolutionary and ecological population dynamics (microbes, phages, etc.), tissue homeostasis (development, cancer, apoptosis)
• collective migration (cells, animals, etc.)

This theme is transverse to the first three. And beyond, many emergent questions in biology, that tend towards a more integrated view of biological systems, lie at their interfaces. This includes in particular the integration of signals of different natures in developmental biology or in various cellular processes, as well as the potential for learning through self-organization. Promoting new exchanges between established communities around these different themes is a central objective of our project.

Each of these questions about biological systems potentially calls for the integration of a very broad spectrum of skills: biology, theoretical and experimental physics, engineering, chemistry or nanochemistry, etc. The ambition of the AQV research network is to a serve as a hub for researchers of diverse backgrounds who are engaged in or wish to engage in interdisciplinary research.