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Biology subjects

Arzash, S.

Publications and source records attributed to Arzash, S..

3 recordsLinked to original sources

Learning Epithelial Elasticity via Local Tension Remodeling

Biological materials, like epithelial tissues, exhibit remarkable adaptability to mechanical stresses, dynamically remodeling their structure in response to external and internal forces. A key challenge is understanding how these tissues store a memory of past mechanical stimuli. Here, we investigate this memory using an active Vertex Model of epithelial sheets incorporating a local, mechanosensitive tension-remodeling rule where junctional tension updates depend on strain, acting as a slow, history-dependent variable. We demonstrate three hallmark mechanical consequences of this memory mechanism. First, a localized, short contractile cue permanently reprograms the global shear modulus, with the direction of change (stiffening or softening) controlled by the tension remodeling rate. Second, the tissue stores a long-range mechanical memory: a prior stimulus at one site modulates the tissues response to a subsequent, distant stimulus, mediated by coupling across the entire junctional network. Finally, we show that simple cyclic bulk deformation acts as a training protocol that autonomously tunes the tissues constitutive properties, including programming the Poisson ratio to auxetic (negative) values. These findings position epithelial mechanics within the framework of unsupervised physical learning, identifying the mechanosensitive remodeling rates as powerful control parameters for designing programmable tissue-scale rheology.

biophysics↗

Epithelial convergent extension as a tuning process

Self-tuning--the ability of disordered systems to develop desired collective behaviors by tuning internal couplings in response to feedback--has recently emerged as a powerful framework for understanding adaptation in amorphous solids, mechanical metamaterials, and electrical networks. These systems can learn desired responses, encode memory, and robustly reorganize under repeated stimuli, much like artificial neural networks but without requiring processors to adjust their weights. Here, we extend this paradigm to morphogenesis and show that the epithelium can be viewed as tunable matter and that epithelial convergent extension (CE) can be understood as a self-tuning process. Using a vertex model with active interfacial tensions, we systematically compare distinct tension-update strategies, including externally imposed shear, global gradient descent optimization, and decentralized local feedback rules. We find that while all methods can generate tissue elongation, only local orientation- and length-sensitive rules reproduce key experimental features of CE, such as supracellular actomyosin pattern formation, cell shape changes, and junctional alignment. In contrast, global optimization produces homogeneous tension patterns and mechanically fragile states. By interpreting CE through the lens of tuning, our framework bridges the physics of tunable matter with developmental biology, revealing how simple, local rules enable tissues to efficiently orchestrate complex morphogenetic outcomes through decentralized mechanical adaptation.

biophysics↗

Morphogenesis-on-chip: A minimal in vitro assay for cell intercalation highlights the importance of interfacial tension and migratory forces

Cell intercalation, the dynamic exchange of cellular neighbors, is fundamental to embryonic morphogenesis, tissue homeostasis, and wound healing. Despite extensive study in complex tissues, the minimal mechanical requirements driving intercalation remain poorly understood due to confounding tissue level interactions. Here, we present a novel morphogenesis-on-chip assay utilizing micropatterned cell quadruplets. This system isolates the elementary unit of intercalation while enabling quantitative force and shape measurements. Cross-shaped micropatterns generate stable four cell configurations in MDCK epithelial cells. Surprisingly, these cells spontaneously undergo T1 transitions autonomously. We combined live imaging with force inference and traction force microscopy, which revealed that intercalation emerges from two distinct mechanisms: interfacial tension dynamics and differential cell migration. Specifically, we show a correlation between central junction shrinkage and increased relative tension. Similarly, we show a correlation between central junction shrinkage and migratory forces. We successfully adapted the assay to Xenopus mesoderm cells, revealing conserved mechanical principles across cell types. Furthermore, experimentally derived effective energy landscapes closely match theoretical vertex model predictions, and suggest a dominant role for migratory forces in driving intercalation. This confirms that our minimal system recapitulates the fundamental physics of intercalation. This approach provides the first quantitative framework for studying intercalation mechanics in isolation and establishes a versatile platform for investigating morphogenetic processes. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=73 SRC="FIGDIR/small/662274v2_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@41db6aorg.highwire.dtl.DTLVardef@1ac1cb1org.highwire.dtl.DTLVardef@8fcb2corg.highwire.dtl.DTLVardef@63e320_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗