Biology subjects

Margadant, F.

Publications and source records attributed to Margadant, F..

3 recordsLinked to original sources

bioRxiv2026

SACHET: seeded contour tracking measures Rab conversion kinetics on individual endosomes in live cells

Membrane-labeled endosomes appear as hollow rings in a projection; they move, deform and exchange their coat, which population trackers (tools that detect every object of one kind and link the detections across frames) are not designed to follow. Here we introduce SACHET (Seeded Adaptive Contour & Hollow Endosome Tracking), a human-supervised Fiji tool that tracks one endosome at a time. On simulated ground truth it localizes the center to 10 nm, recovers transition time constants and lags without bias and holds the target among touching neighbors; comparisons with tuned TrackMate and Cellpose delineate where each is superior. In crowded spinning-disk projections, TrackMate followed one of seven marked Rab5-to-Rab7 conversions; supervised SACHET followed all 37. SACHET thus provides a stable per-endosome frame in which membrane morphology and protein exchange can be quantified: in five cell lines the conversion toggles like a digital switch within seconds to minutes, differing between lines.

cell biology↗

bioRxiv2022

Rejuvenating Senescent Cells and Organisms with Only Ultrasound

The presence of an appreciable number of senescent cells causes age-related pathologies as their removal by genetic or pharmacological means, as well as possibly by exercise, improves outcome in animal models. An alternative to depleting such cells would be to rejuvenate them to promote their return to a replicative state. Means to do so have not been explored, but here we report that treatment of non-growing senescent cells with low-frequency ultrasound (LFU) rejuvenates the cells. Notably, we find 15 characteristics of senescent cells that are reversed by LFU, including decreased cell and organelle motility. Mechanistically, LFU causes Ca2+ entry that precedes dramatic increases in autophagy and an inhibition of mTORC1 signaling and the movement of Sirtuin1 from the nucleus to cytoplasm. Also, there is inhibition of SASP secretion, as well as {beta}-galactosidase expression, telomere length is increased, while nuclear 5mc, H3K9me3, {gamma}H2AX, nuclear p53, ROS and mitoROS levels are all restored to normal levels. Repeated LFU treatments enables expansion of primary cells and stem cells beyond normal replicative limits without altering their phenotype. The rejuvenation process is enhanced by co-treatment with rapamycin or Rho kinase inhibition but is inhibited by blocking Sirtuin1 or Piezo1 activity. We further optimized the LFU treatment parameters to increase mouse lifespan and healthspan. These results suggest that mechanically-induced pressure waves alone can reverse senescence and aging effects at the cellular and organismal level, providing a non-pharmacological way to treat the effects of aging. One-Sentence SummaryLow frequency ultrasound is sufficient to rejuvenate senescent cells by activating autophagy in aged mice to improve healthspan.

physiology↗

bioRxiv2020

Ultrasound-mediated mechanical forces selectively kill tumor cells

Ultrasound has been used to target tumors either through local heating or local nanobubbles but these methods damage surrounding normal cells in the target area. Recent studies show that tumor cells are susceptible to mechanical stresses and undergo calcium-dependent apoptosis under conditions that promote normal cell growth. Here we report that low-frequency ultrasound causes apoptosis of tumor cells by activating a calpain-dependent mitochondrial pathway that depends upon calcium entry through the mechanosensitive Piezo1 channels. This is a general property of all tumor cell lines tested so far irrespective of tissue origin. In animals, ultrasound irradiation causes tumor killing in the chick chorioallantoic membrane (CAM) model with relatively little damage to the chick embryos. Further, patient-derived pancreatic tumor organoids are killed by ultrasound treatment. Because low-level ultrasound causes apoptosis of tumor cells from many different tissues in different microenvironments, it may offer a safe non-invasive approach to augment tumor treatments.

cancer biology↗