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Biology subjects

Heydecker, M.

Publications and source records attributed to Heydecker, M..

3 recordsLinked to original sources

Intravital single-molecule imaging reveals cytoskeletal turnover as a driver of membrane remodeling in live animals

Understanding how cells regulate plasma membrane architecture inside intact living organs in a live animal has been limited by the inability to directly measure molecular dynamics in vivo. Here we introduce intravital single-molecule microscopy (iSiMM), an imaging approach that enables tracking of individual, endogenously expressed cytoskeletal components at the plasma membrane in live mice. Applying iSiMM to murine acinar secretory cells, we identify discrete basolateral membrane domains built on deeply folded membrane infolds that function as a pre-existing membrane reservoir. Single-molecule measurements reveal continuous, regulated molecular turnover within these domains. Physiological stimulation accelerates cytoskeletal exchange promoting rapid membrane unfolding and cell expansion. Together, these findings establish iSiMM as a general strategy for probing molecular kinetics underlying dynamic cellular behaviors in intact organs. One-sentence summaryIntravital single-molecule microscopy enables direct measurement of molecular kinetics underlying dynamic cellular behaviors in intact living organs.

cell biology↗

Longitudinal Imaging of the Premalignant Tumor Microenvironment Reveals Transient Myeloid States Predictive of Tumor Fate

The spontaneous regression of cancer lesions illustrates the power of immune surveillance; yet these transient events have largely escaped systematic analysis. Using longitudinal intravital microscopy in a carcinogen-induced model of head and neck cancer, we followed premalignant lesions within the same animals for 24 weeks at single-cell resolution. This strategy uncovered three trajectories: progression, stability, or regression, and enabled direct analysis of immune dynamics underlying each fate. Lesion outcome was determined by the spatial organization of myeloid-derived antigen-presenting cells: regressing lesions were characterized by dense clusters of myeloid-derived cells associated with CXCL9+/CXCL10+ expression and T cell recruitment, whereas progressing lesions displayed a scattered infiltration of these cells. Remarkably, transient myeloid clusters arose prior to any detectable lesion formation and marked regions that would later develop into premalignant lesions. These findings identify spatiotemporal myeloid organization as an early determinant of tumor fate and provide a mechanistic framework for predicting and intercepting cancer at its inception. Summary SentenceEarly myeloid architecture dictates cancer fate: dense CXCL9/CXCL10 clusters with T-cell enrichment accompany regression, whereas sparse infiltration predicts progression. Transient pre-lesional myeloid clusters emerge at future tumor sites, revealing immune organization as an early determinant of malignancy.

cancer biology↗

Spatial and Temporal Coordination of Force-generating Actin-based Modules Drives Membrane Remodeling In Vivo

Membrane remodeling drives a broad spectrum of cellular functions, and it is regulated through mechanical forces exerted on the membrane by cytoplasmic complexes. Here, we investigate how actin filaments dynamically tune their structure to control the active transfer of membranes between cellular compartments with distinct compositions and biophysical properties. Using intravital subcellular microscopy in live rodents we show that: a lattice composed of linear filaments stabilizes the granule membrane after fusion with the plasma membrane; and a network of branched filaments linked to the membranes by Ezrin, a regulator of membrane tension, initiates and drives to completion the integration step. Our results highlight how the actin cytoskeleton tunes its structure to adapt to dynamic changes in the biophysical properties of membranes.

cell biology↗