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The physics of active matter and active liquid crystals has emerged as a key modelling tool across cell and tissue biology in understanding the form and origin of mechanical forces and identifying subtle forms of order and topological defects in cell cultures and tissues. Living systems are commonly chiral, from constituent biopolymers to large scale morphology, however the interplay between chirality and mechanics is still in a largely nascent state. I will describe our recent work on chiral mechanics in active liquid crystals and in membranes. Both display a geometric form of odd elasticity in response to mean curvature gradients but directed perpendicularly. This results in an array of fluid vortices, that are tunable by mechanical strain, in the liquid crystal case and to persistent surface flows and twisting shape instability in membranes. This is joint work with SJ Kole, Ananyo Maitra, Sriram Ramaswamy, and Sami Al-Izzi.

A fundamental characteristic of life is its ubiquity across diverse environments. At the core of this ubiquity lies cellular metabolism, an interconnected network of chemical reactions that transforms environmental nutrients into the mass and free energy that support growth. Metabolism is highly versatile, manifested by life’s spread in environments spanning a wide range of nutrient types, reducing agents, temperatures, pH, and other physicochemical parameters. Metabolic versatility can be achieved by both, evolutionary adaptation as well as phenotypic plasticity. Because the matter and energy fluxes sustained by metabolism keep cells far from thermodynamic equilibrium, it has long been speculated that dissipation poses essential constraints to cellular growth and evolutionary adaptations as well as phenotypic plasticity. Here, I will discuss our collaborative data-driven approach to infer the thermodynamics of unicellular growth by parsing existing data from more than 400 instances of balanced unicellular growth and analyze them using a minimal non-equilibrium thermodynamics framework. I will elaborate on our findings that despite vast variability in biomass yield and dissipation across all domains of life and metabolic diversity, the dissipative cost of growth is largely conserved. Within this conserved cost, aerobic respiration is singled out by its high thermodynamic efficiency. Our results are consistent with a model whereby dissipation imposes a strong constraint on cellular life and suggest that evolutionary pressure on thermodynamic efficiency may have been one of the drivers behind widespread aerobic respiratory metabolism across life.

In the inner ear, mechanosensitivity of the hair cells results from direct mechanical activation of ion channels by the tip links of their hair bundle. Sound-evoked deflection of the hair bundle modulates tip-link tension, resulting in channel gating and a transduction current. Reciprocally, channel gating feeds back on tip-link tension, producing an internal force called the “gating force”. The gating force is a fundamental determinant of hair-cell mechanosensitivity, for its magnitude sets the maximal slope of the sigmoidal relationship between the transduction current and the hair-bundle displacement. Moreover, gating forces can be large enough to effectively reduce the hair bundle’s stiffness, even resulting in negative stiffness. Through an active dynamic interplay with adaptation, negative stiffness fosters spontaneous oscillations of the hair bundle and nonlinear amplification of sinusoidal stimuli. Despite its importance for hair-cell mechanosensitivity, the biophysical and molecular determinants of the gating force remain poorly understood. In this talk, I will show that the electric potential in endolymph bathing the hair bundles can serve as a control parameter of the gating force. Our work further indicates that the molecular movement associated to channel gating—the gating swing—can be of variable magnitude in the same hair cell depending on electrical conditions.

Precise periodic organization of cells is required for the function of many organs and tissues. It is often unclear, however, how such precise patterns emerge during embryonic development. We study this question in the context of the mammalian inner ear, one of the most intricate organs of the mammalian body plan. The mammalian hearing and balance organs contain precisely positioned arrays of alternating sensory hair cells and nonsensory supporting cells. How such precise alternating patterns emerge during embryonic development and what factors regulate their regeneration in adults are not well understood. In the first part of the talk I will give an introduction to fine grained patterning processes during embryonic development and introduce the inner ear as a model system. In the second part of the talk I will discuss two research topics: First, I will discuss how a single row of alternating inner hair cells and supporting cells in the cochlea emerge from an initially undifferentiated fields of cells. Second, I will talk about our effort to understand why mice lose the ability regenerate hair cells within the first few weeks after birth. For both topics, we combine live imaging of inner ear explants, laser ablation of single cells, mechanical perturbations, and mathematical and biophysical modelling to elucidate how mechanics and regulatory process coordinate to control developmental and regenerative programs. Overall, our work highlights the role of coordination between differentiation and mechanics during hair cell development and regeneration.

All organisms perform multiple tasks, such as growth, homeostasis, and reproduction. To survive and thrive in the face of competition for finite resources, all organisms evolve to invest energy in traits that maximize their fitness (i.e., reproductive success) within their environment, resulting in trade-offs. These trade-offs are expected to change throughout an organism's life cycle since young and old individuals have different functional demands. The mechanisms of such life history trade-offs are not well understood. Multicellular systems comprise many morphologically and functionally specialized cell types that uniquely influence an organism's ability to perform tasks. Thus, analyzing cellular composition at the organismal level could reveal key biological processes associated with life history traits and potential trade-offs. Here, I will discuss our efforts to use a concept from engineering and economics, Pareto optimality theory, to explore the possibility of inferring life history traits, their trade-offs, and potential regulatory mechanisms from high-dimensional organismal-scale single-cell transcriptomics of planarian flatworms, as well as the prospect of using the extensive functional genomics toolkit of planarians to directly test predicted cause-effect relationships.