Cell Geometry Limits Bacterial Metabolic Efficiency.

Bacterial metabolic strategies are fundamentally linked to their physical form, yet a quantitative understanding of how cell size and shape constrain the efficiency of biomass production remains poorly understood. Here, we develop a coarse-grained whole-cell model of bacterial physiology that integrates proteome allocation, metabolic fluxes, and cell geometry with physical limits on cell surface area and intracellular diffusion. Our model shows that the efficiency of cellular growth is not monotonic with nutrient availability; instead, it peaks precisely at the onset of overflow metabolism, framing this metabolic switch as an optimal tradeoff between efficient use of imported nutrients and rapid growth.

Design principles and feedback mechanisms in organelle size control.

Intracellular organelles are essential for cellular architecture and function, and their size regulation is critical for maintaining cellular homeostasis. Organelle size often scales with cell size, governed by mechanisms that integrate resource allocation, stochastic dynamics, and feedback controls. Here we review these underlying biophysical principles of organelle size control, including the limiting pool hypothesis, stochastic assembly processes, and feedback-driven growth dynamics.

Mechanistic basis for non-exponential bacterial growth.

Bacterial populations typically exhibit exponential growth under resource-rich conditions, yet individual cells often deviate from this pattern. Recent work has shown that the elongation rates of and increase throughout the cell cycle (super-exponential growth), while displays a mid-cycle minimum (convex growth), and grows linearly. Here, we develop a single-cell model linking gene expression, proteome allocation, and mass growth to explain these diverse growth trajectories.

Catalytic growth in a shared enzyme pool ensures robust control of centrosome size.

Accurate regulation of centrosome size is essential for ensuring error-free cell division, and dysregulation of centrosome size has been linked to various pathologies, including developmental defects and cancer. While a universally accepted model for centrosome size regulation is lacking, prior theoretical and experimental works suggest a centrosome growth model involving autocatalytic assembly of the pericentriolar material. Here, we show that the autocatalytic assembly model fails to explain the attainment of equal centrosome sizes, which is crucial for error-free cell division.

Anisotropic Cell Shape and Motion Coordinate Hindbrain Neuropore Morphogenesis.

Neural tube closure is a critical morphogenetic process in vertebrate development, and failure to close cranial regions such as the hindbrain neuropore (HNP) leads to severe congenital malformations. While mechanical forces like actomyosin purse-string contraction and directional cell crawling have been implicated in driving HNP closure, how these forces organize local cell shape and motion to produce large-scale tissue remodeling remains poorly understood. Using live and fixed imaging of mouse embryos combined with cell-based biophysical modeling, we show that these force-generating mechanisms are insufficient to explain the robust patterns of cell elongation and nematic alignment observed at the HNP border.

Tension Remodeling Regulates Topological Transitions in Epithelial Tissues.

Cell neighbor exchanges play a critical role in regulating tissue fluidity during epithelial morphogenesis and repair. , these neighbor exchanges are often hindered by the formation of transiently stable fourfold vertices, which can develop into complex multicellular rosettes where five or more cell junctions meet. Despite their importance, the mechanical origins of multicellular rosettes have remained elusive, and current cellular models lack the ability to explain their formation and maintenance.

Gene Expression Tradeoffs Determine Bacterial Survival and Adaptation to Antibiotic Stress.

To optimize their fitness, cells face the crucial task of efficiently responding to various stresses. This necessitates striking a balance between conserving resources for survival and allocating resources for growth and division. The fundamental principles governing these tradeoffs is an outstanding challenge in the physics of living systems.

Proliferation symmetry breaking in growing tissues.

Morphogenesis of developing tissues results from anisotropic growth, typically driven by polarized patterns of gene expression. Here we propose an alternative model of anisotropic growth driven by self-organized feedback between cell polarity, mechanical pressure, and cell division rates. Specifically, cell polarity alignment can induce spontaneous symmetry breaking in proliferation, resulting from the anisotropic distribution of mechanical pressure in the tissue.

Mechanical and biochemical feedback combine to generate complex contractile oscillations in cytokinesis.

The actomyosin cortex is an active material that generates force to drive shape changes via cytoskeletal remodeling. Cytokinesis is the essential cell division event during which a cortical actomyosin ring closes to separate two daughter cells. Our active gel theory predicted that actomyosin systems controlled by a biochemical oscillator and experiencing mechanical strain would exhibit complex spatiotemporal behavior.

Differential growth regulates asymmetric size partitioning in .

Cell size regulation has been extensively studied in symmetrically dividing cells, but the mechanisms underlying the control of size asymmetry in asymmetrically dividing bacteria remain elusive. Here, we examine the control of asymmetric division in , a bacterium that produces daughter cells with distinct fates and morphologies upon division. Through comprehensive analysis of multi-generational growth and shape data, we uncover a tightly regulated cell size partitioning mechanism.

Growth-induced collective bending and kinetic trapping of cytoskeletal filaments.

Growth and turnover of actin filaments play a crucial role in the construction and maintenance of actin networks within cells. Actin filament growth occurs within limited space and finite subunit resources in the actin cortex. To understand how filament growth shapes the emergent architecture of actin networks, we developed a minimal agent-based model coupling filament mechanics and growth in a limiting subunit pool.

Interplay of condensate material properties and chromatin heterogeneity governs nuclear condensate ripening.

Nuclear condensates play many important roles in chromatin functions, but how cells regulate their nucleation and growth within the complex nuclear environment is not well understood. Here, we report how condensate properties and chromatin mechanics dictate condensate growth dynamics in the nucleus. We induced condensates with distinct properties using different proteins in human cell nuclei and monitored their growth.

Mechanical control of cell proliferation patterns in growing epithelial monolayers.

Cell proliferation plays a crucial role in regulating tissue homeostasis and development. However, our understanding of how cell proliferation is controlled in densely packed tissues is limited. Here we develop a computational framework to predict the patterns of cell proliferation in growing epithelial tissues, connecting single-cell behaviors and cell-cell interactions to tissue-level growth.

Gene expression tradeoffs determine bacterial survival and adaptation to antibiotic stress.

To optimize their fitness, cells face the crucial task of efficiently responding to various stresses. This necessitates striking a balance between conserving resources for survival and allocating resources for growth and division. The fundamental principles governing these tradeoffs is an outstanding challenge in the physics of living systems.

Energy allocation theory for bacterial growth control in and out of steady state.

Efficient allocation of energy resources to key physiological functions allows living organisms to grow and thrive in diverse environments and adapt to a wide range of perturbations. To quantitatively understand how unicellular organisms utilize their energy resources in response to changes in growth environment, we introduce a theory of dynamic energy allocation which describes cellular growth dynamics based on partitioning of metabolizable energy into key physiological functions: growth, division, cell shape regulation, energy storage and loss through dissipation. By optimizing the energy flux for growth, we develop the equations governing the time evolution of cell morphology and growth rate in diverse environments.

Excitable dynamics driven by mechanical feedback in biological tissues.

Pulsatory activity patterns, driven by mechanochemical feedback, are prevalent in many biological systems. However, the role of cellular mechanics and geometry in the propagation of pulsatory signals remains poorly understood. Here we present a theoretical framework to elucidate the mechanical origin and regulation of pulsatile activity patterns within excitable multicellular tissues.

Mechanical positive feedback and biochemical negative feedback combine to generate complex contractile oscillations in cytokinesis.

Contractile force generation by the cortical actomyosin cytoskeleton is essential for a multitude of biological processes. The actomyosin cortex behaves as an active material that drives local and large-scale shape changes via cytoskeletal remodeling in response to biochemical cues and feedback loops. Cytokinesis is the essential cell division event during which a cortical actomyosin ring generates contractile force to change cell shape and separate two daughter cells.

Mechanical control of cell proliferation patterns in growing tissues.

Cell proliferation plays a crucial role in regulating tissue homeostasis and development. However, our understanding of how cell proliferation is controlled in densely packed tissues is limited. Here we develop a computational framework to predict the patterns of cell proliferation in growing tissues, connecting single-cell behaviors and cell-cell interactions to tissue-level growth.

Dynamic proteome trade-offs regulate bacterial cell size and growth in fluctuating nutrient environments.

Bacteria dynamically regulate cell size and growth to thrive in changing environments. While previous studies have characterized bacterial growth physiology at steady-state, a quantitative understanding of bacterial physiology in time-varying environments is lacking. Here we develop a quantitative theory connecting bacterial growth and division rates to proteome allocation in time-varying nutrient environments.

Membrane tension induces F-actin reorganization and flow in a biomimetic model cortex.

The accumulation and transmission of mechanical stresses in the cell cortex and membrane determines the mechanics of cell shape and coordinates essential physical behaviors, from cell polarization to cell migration. However, the extent that the membrane and cytoskeleton each contribute to the transmission of mechanical stresses to coordinate diverse behaviors is unclear. Here, we reconstitute a minimal model of the actomyosin cortex within liposomes that adheres, spreads and ultimately ruptures on a surface.

Super-exponential growth and stochastic size dynamics in rod-like bacteria.

Proliferating bacterial cells exhibit stochastic growth and size dynamics, but the regulation of noise in bacterial growth and morphogenesis remains poorly understood. A quantitative understanding of morphogenetic noise control, and how it changes under different growth conditions, would provide better insights into cell-to-cell variability and intergenerational fluctuations in cell physiology. Using multigenerational growth and width data of single Escherichia coli and Caulobacter crescentus cells, we deduce the equations governing growth and size dynamics of rod-like bacterial cells.