Biology subjects

Callan-Jones, A.

Publications and source records attributed to Callan-Jones, A..

5 recordsLinked to original sources

bioRxiv2026

Curvature-guided chiral collective organization of myoblast tissues

Surface curvature is a fundamental geometric cue in tissue morphogenesis, yet its role in guiding collective cell organization has remained elusive. Here, we show that curvature acts as a geometric control parameter that shapes supracellular alignment and chirality while modulating myogenic differentiation in myoblast tissues. Cells cultured on curved substrates self-organize into robust helical assemblies whose handedness is set, and can be reversed, by the sign of curvature: convex fibers produce right-handed helices, whereas concave channels invert the chirality. We identify a previously hidden clockwise bias in single-cell motion associated with the helical actin cytoskeleton. A minimal continuum theory coupling an effective chiral drive to curvature quantitatively captures the emergence and reversal of tissue-scale chiral alignment. On substrates with spatially varying curvature, local curvature gradients organize patterned multicellular architectures while preserving a global handedness. Curvature is also associated with myogenic state, with higher curvature linked to reduced or delayed differentiation. Together, these findings reveal how complex geometries shape the alignment, symmetry, and cellular state of living tissues.

biophysics↗

bioRxiv2025

Power-law decay of force on cell membrane tethers reflects long-ranged relaxation of membrane tension

Membrane tension is an acknowledged regulator of a wide array of cell functions; however, whether it acts locally or globally in different contexts remains debated. Recent experiments that locally perturb tension and measure the response elsewhere on the membrane are not conclusive, and the mechanism of diffusive tension relaxation has been called into doubt. Here, we consider the tension response to a sudden extension of a membrane tether, and report a quantitative signature of dynamic tension relaxation, which up to now is missing. We present a theory based on tension diffusion leading to a prediction of power-law decay in time of the force holding the tether, with a material-independent exponent of 1/3. This prediction is confirmed to within a few percent by re-analyzing eleven sets of tether data from two cell types with distinct membrane cortical architectures. Overall, our scaling results indicate the absence of a relevant characteristic length and therefore generically reflect tension relaxation by long-range membrane lipid flows.

biophysics↗

bioRxiv2019

Adhesion-free cell migration by topography-based force transduction

Eukaryotic cells migrate by coupling the intracellular force of the actin cytoskeleton to the environment. While force-coupling is usually mediated by transmembrane adhesion receptors, especially these of the integrin family, amoeboid cells like leukocytes can migrate extremely fast despite very low adhesive forces1. We show that leukocytes cannot only migrate under low adhesion but indeed can transduce forces in the complete absence of transmembrane force coupling. When confined within three-dimensional environments, they use the topographic features of the substrate to propel themselves. Here, the retrograde flow of the actin cytoskeleton follows the texture of the substrate, creating shear forces sufficient to drive deformations towards the back of the cell. Notably, adhesion dependent and adhesion independent migration are not exclusive but rather variants of the same principle of coupling retrograde actin flow to the environment and thus can potentially operate simultaneously. As adhesion free migration is independent of the chemical composition of the environment it renders cells completely autonomous in their locomotive behavior.

cell biology↗

bioRxiv2019

The roles of microtubules and membrane tension in axonal beading, retraction, and atrophy

Axonal beading--formation of a series of swellings along the axon--and retraction are commonly observed shape transformations that precede axonal atrophy in Alzheimers, Parkinson, and other neurodegenerative conditions. The mechanisms driving these morphological transformations are poorly understood. Here we report controlled experiments which can induce either beading or retraction and follow the time evolution of these responses. By making quantitative analysis of the shape modes under different conditions, measurement of membrane tension, and using theoretical considerations, we argue that membrane tension is the main driving force that pushes cytosol out of the axon when microtubules are degraded, causing axonal thinning. Under pharmacological perturbation, atrophy is always retrograde and this is set by a gradient in the microtubule stability. The nature of microtubule depolymerization dictates the type of shape transformation vis a vis beading or retraction. Elucidating the mechanisms of these shape transformations will facilitate development of strategies to prevent or arrest axonal atrophy due to neurodegenerative conditions.

biophysics↗

bioRxiv2019

The axonal actin-spectrin lattice acts as shock absorbers to protect neurons from stretch-induced damage

Axons are thin tubular extensions generated by neuronal cells to transmit signals across long distances. In the peripheral and the central nervous systems, axons experience large deformations during normal activity or as a result of injury. Yet, axon biomechanics, and its relation to the internal structure that allows axons to withstand such deformations, is poorly understood. Up to now, it has been generally assumed that microtubules and their associated proteins are the major load-bearing elements in axons. We revise this view point by combining mechanical measurements using a custom developed force apparatus with biochemical or genetic modifications to the axonal cytoskeleton, revealing an unexpected role played by the actin-spectrin skeleton. For this, we first demonstrate that axons exhibit a reversible strain-softening response, where its steady state elastic modulus decreases with increasing strain. We then explore the contributions from the various cytoskeletal components of the axon, and show that the recently discovered membrane-associated skeleton consisting of periodically spaced actin filaments interconnected by spectrin tetramers play a prominent mechanical role. Finally, using a theoretical model we argue that the actin-spectrin skeleton act as an axonal tension buffer by reversibly unfolding repeat domains of the spectrin tetramers to buffer excess mechanical stress.

biophysics↗