Biology subjects

Koning, K.

Publications and source records attributed to Koning, K..

4 recordsLinked to original sources

bioRxiv2024

Alterations in large-scale resting-state network nodes following transcranial focused ultrasound of deep brain structures

BackgroundLow-intensity transcranial focused ultrasound (tFUS) is a brain stimulation approach that holds immense promise for the treatment of brain-based disorders. Several studies in humans have shown that tFUS can successfully modulate perfusion in focal sonication targets including the amygdala; however, limited research has explored how tFUS impacts the function of large-scale neural networks. ObjectiveThe aim of the current study was to address this gap and examine changes in resting-state connectivity between large-scale network nodes using a randomized, double-blind, within-subject crossover study design. MethodsHealthy adults (n=18) completed two tFUS sessions, 14 days apart. Each session included tFUS of either the right amygdala or the left entorhinal cortex (ErC). The inclusion of two active targets allowed for within-subjects comparisons as a function of the locus of sonication. Resting-state functional magnetic resonance imaging was collected before and after each tFUS session. ResultstFUS altered resting-state functional connectivity (rsFC) within and between rs-network nodes. Specifically, pre-to-post sonication of the right amygdala modulated connectivity within nodes of the salience network (SAN) and between nodes of the SAN and the default-mode network (DMN) and fronto-parietal network (FRP). A decrease in SAN to FPN connectivity was specific to the amygdala target. Pre-to-post sonication of the left ErC was found to modulate connectivity between the dorsal attention network (DAN) and FPN and DMN. An increase in DAN to DMN connectivity was specific to the ErC target. ConclusionThese preliminary findings may suggest that tFUS induces neuroplastic changes beyond the immediate sonication target.

neuroscience↗

bioRxiv2023

Mechanosensitive recruitment of Vinculin maintains junction integrity and barrier function at epithelial tricellular junctions

Apical cell-cell junctions, including adherens junctions (AJs) and tight junctions (TJs), adhere epithelial cells to one another and regulate selective permeability at both bicellular junctions (BCJs) and tricellular junctions (TCJs). Although several specialized proteins are known to localize at TCJs, it remains unclear how actomyosin-mediated tension transmission at TCJs contributes to the maintenance of junction integrity and barrier function at these sites. Here, utilizing gastrula-stage Xenopus laevis embryos as a model system, we describe a mechanism by which Vinculin, a mechanosensitive protein, anchors the actomyosin network at TCJs, thus maintaining TJ stability and barrier function. Using an optogenetic approach, we found that acutely increasing junctional tension results in robust recruitment of Vinculin to apical junctions immediately surrounding TCJs. In Vinculin knockdown (KD) embryos, junctional actomyosin intensity is decreased and becomes disorganized at TCJs. Using fluorescence recovery after photobleaching (FRAP), we show that loss of Vinculin results in reduced Actin stability at TCJs. Vinculin knockdown also destabilizes Angulin-1, a key protein involved in regulating barrier function at TCJs. When Vinculin KD embryos are subjected to increased tension, TCJs cannot maintain their proper morphology. Finally, using a live imaging barrier assay, we detect increased barrier leaks at TCJs in Vinculin KD embryos. Together, our findings show that Vinculin-mediated actomyosin organization is required to maintain junction integrity and barrier function at TCJs and reveal new information about the interplay between adhesion and barrier function at TCJs. HighlightsO_LIVinculin is mechanosensitively recruited to tricellular junctions C_LIO_LIVinculins actin-binding function is needed for tricellular actomyosin organization C_LIO_LITricellular tight junctions are unstable when Vinculin is knocked down C_LIO_LIVinculin is required to maintain barrier function at tricellular junctions C_LI

cell biology↗

bioRxiv2023

Matrix stiffness modulates 3D spheroid sorting and burst-like collective migration

While it is known that cells with differential adhesion tend to segregate and preferentially sort, the physical forces governing sorting and invasion in heterogeneous tumors remain poorly understood. To investigate this, we tune matrix confinement, mimicking changes in the stiffness and confinement of the tumor microenvironment, to explore how physical confinement influences individual and collective cell migration in 3D spheroids. High levels of confinement lead to cell sorting while reducing matrix confinement triggers the collective fluidization of cell motion. Cell sorting, which depends on cell-cell adhesion, is crucial to this phenomenon. Burst-like migration does not occur for spheroids that have not undergone sorting, regardless of the degree of matrix confinement. Using computational Self-Propelled Voronoi modeling, we show that spheroid sorting and invasion into the matrix depend on the balance between cell-generated forces and matrix resistance. The findings support a model where matrix confinement modulates 3D spheroid sorting and unjamming in an adhesion-dependent manner, providing insights into the mechanisms of cell sorting and migration in the primary tumor and toward distant metastatic sites.

biophysics↗

bioRxiv2021

Endoplasmic Reticulum morphological regulation by RTN4/NOGO modulates neuronal regeneration by slowing luminal transport

Cell and tissue functions rely on an elaborate intracellular transport system responsible for distributing bioactive molecules with high spatiotemporal accuracy. The tubular network of the Endoplasmic Reticulum (ER) constitutes a system for the delivery of luminal solutes it stores, including Ca2+, across the cell periphery. The physical nature and factors underlying the ERs functioning as a fluidics system are unclear. Using an improved ER transport visualisation methodology combined with optogenetic Ca2+ dynamics imaging, we observed that ER luminal transport is modulated by natural ER tubule narrowing and dilation, directly proportional to the amount of an ER membrane morphogen, Reticulon 4 (RTN4). Consequently, the ER morphoregulatory effect of RTN4 defines ERs capacity for peripheral Ca2+ delivery and thus controls axonogenesis. Excess RTN4 limited ER luminal transport, Ca2+ release and iPSC-derived cortical neurons axonal extension, while RTN4 elimination reversed the effects. SummaryIntracellular transport through the lumen of the ER network is modulated through narrowing/dilation of ER tubules by a membrane morphogen - RTN4, a process controlling axonogenesis by limiting the delivery of ER-stored Ca2+.

cell biology↗