Biology subjects

Martens, T.

Publications and source records attributed to Martens, T..

3 recordsLinked to original sources

bioRxiv2024

Active foam dynamics of tissue spheroid fusion

Three-dimensional tissue spheroids are a key building block in biofabrication, yet the link between their material properties and active mechanics of individual cells is not fully understood. We study the material properties of small spheroids of human periosteum-derived cells as they effect spheroid fusion, an elementary operation for constructing large tissue structures. We use two-photon confocal microscopy to measure cell-cell tension and individual cell motility throughout fusion. Cytoskeletal inhibition through Y-27632 (ROCKi) results in more granular tissues with decreased cell rearrangements, but accelerated fusion. Further reducing cell contractility with blebbistatin and ROCKi increases tissue granularity, decreases rearrangements, and slows down fusion. In all conditions, complete fusion is associated with frequent cellular rearrangements. Using a novel computational model that represents tissue material as an active cellular foam, with cells depicted as viscous shells with interfacial tension and persistent, random motility, we construct a phase diagram of spheroid fusion in function of relative cell-cell tension and cell motility. Our results reveal a close relationship between microscopic tissue fluidity and the visco-elastic properties of spheroid fusion. Additionally, we find that cell-cell friction promotes arrested fusion by inducing jamming through a distinct physical mechanism. Combined, our findings offer a framework for understanding spheroid fusion dynamics that can aid in the robust generation of large tissue constructs for regenerative medicine.

biophysics↗

bioRxiv2022

Neuro-immune Crosstalk in the Enteric Nervous System from Early Postnatal Development to Adulthood

Correct development and maturation of the enteric nervous system (ENS) is critical for survival. Early in life, the ENS requires significant refinement in order to adapt to the evolving needs of the tissue, changing from milk to solid food at the time of weaning. Here, we demonstrate that resident macrophages of the muscularis externa, MM{phi}, refine the ENS early in life by pruning synapses and phagocytosing abundant enteric neurons. After weaning, MM{phi} continue to closely interact with the ENS, acquire a microglia-like phenotype and are crucial for the survival of enteric neurons. Of note, this microglia-like phenotype is instructed by TGF{beta} produced by the ENS, introducing a novel reciprocal cell-cell communication responsible for the maintenance of the neuron-associated MM[FE] niche in the gut. These findings elucidate a novel role of intestinal macrophages in ENS refinement early in life, and open new opportunities to treat intestinal neurodegenerative disorders by manipulating the ENS-macrophage niche.

immunology↗

bioRxiv2020

Nano-positioning and tubuline conformation determine transport of mitochondria along microtubules

Correct spatiotemporal distribution of organelles and vesicles is crucial for healthy cell functioning and is regulated by intracellular transport mechanisms. Controlled transport of bulky mitochondria is especially important in polarized cells such as neurons that rely on these organelles to locally produce energy and buffer calcium. Mitochondrial transport requires and depends on microtubules which fill much of the available axonal space. How mitochondrial transport is affected by their position within the microtubule bundles is not known. Here, we found that anterograde transport, driven by kinesin motors, is susceptible to the molecular conformation of tubulin both in vitro and in vivo. Anterograde velocities negatively correlate with the density of elongated tubulin dimers, similar to GTP-tubulin, that are more straight and rigid. The impact of the tubulin conformation depends primarily on where a mitochondrion is positioned, either within or at the rim of microtubule bundle. Increasing elongated tubulin levels lowers the number of motile anterograde mitochondria within the microtubule bundle and increases anterograde transport speed at the microtubule bundle rim. We demonstrate that the increased kinesin step processivity on microtubules consisting of elongated dimers underlies increased mitochondrial dynamics. Our work indicates that the molecular conformation of tubulin controls mitochondrial motility and as such locally regulates the distribution of mitochondria along axons.

neuroscience↗