Biology subjects

Slater, B.

Publications and source records attributed to Slater, B..

3 recordsLinked to original sources

bioRxiv2026

Durotactic Migration Driven by Anisotropic Matrix Stiffening and Mechanical Feedback

Cell migration is fundamental to various biological processes, including morphogenesis, wound healing, and cancer metastasis. Durotaxis--directed migration of cells in response to spatial variations in stiffness--has been extensively studied using engineered substrates with prescribed stiffness. However, recent work has increasingly shifted toward understanding cell migration in fibrous matrices that can be actively remodeled by the actomyosin contractility, as commonly observed in tumor and epithelial cells. Despite these advances, a theoretical framework explaining how cells structurally remodel their surrounding matrix to promote their own durotaxis, and which cellular forces govern this behavior, remains elusive. To address this gap, we developed a biomechanical model in which polarized cells contract and migrate over a fibrous matrix. Using this model, we first confirmed that cells on an externally strained matrix preferentially migrate along the direction of applied strain. Then, we investigated how cells autonomously remodel the matrix to create stiffness patterns favorable for durotaxis. In the presence of intercellular adhesion, cells acted collectively to stiffen the matrix, after which a small subset of cells escaped the main population and migrated outward. This behavior is reminiscent of intravasation during cancer metastasis, where cohesive cell clusters generate local matrix remodeling that facilitates the departure of more motile subpopulations. These results illustrate how matrix stiffening driven by cell cohesion and contractility regulates durotactic behavior and provide mechanistic insight into collective invasion processes relevant to cancer metastasis.

biophysics↗

bioRxiv2025

Insulin-like peptides play distinct roles in nutrient-dependent plasticity in Drosophila

The highly conserved insulin signalling pathway regulates growth and development time in response to nutrition across metazoans. The fruit fly, Drosophila melanogaster has eight insulin-like peptides, which are differentially expressed across development time, organs, and with nutritional conditions. However, whether individual insulin-like peptides play specific roles in controlling growth remains unknown. Recent studies have revealed that the ratio of protein to carbohydrates in the diet plays a key role in regulating life history traits, rather than the total caloric content of the diet alone. Furthermore, individual insulin-like peptides vary in their expression profiles according to nutrient conditions. Whether these differences in expression have any functional significance to animal life history traits remains unclear. Here we report that reducing the protein content of the larval diet through macronutrient restriction - where the calories lost from protein dilution are offset by increased carbohydrate content - results in a more pronounced developmental delay compared to caloric restriction - where both protein and carbohydrate concentrations are reduced. We further reveal that these two diet types result in notable differences in the expression levels of Drosophila insulin-like peptides 2, 3 and 5, and observe distinct phenotypic responses of individual insulin-like peptide mutants raised on each diet type. Taken together, our findings highlight the distinct roles of individual insulin-like peptides in regulating growth and development time in response to changes in dietary macronutrients, and provide key insights into the molecular mechanisms controlling nutritional plasticity in Drosophila. ARTICLE SUMMARYThe insulin signaling pathway regulates growth and development in response to nutrition across metazoans. In the fruit fly, Drosophila melanogaster, seven insulin-like peptides have been identified that bind to a single insulin receptor, however their specific roles remain unclear. This study shows that reducing the protein content of the diet in different ways results in striking differences in the expression patterns of insulin-like peptides and different phenotypic responses of individual mutants raised on these diets. Together, these findings highlight the distinct roles insulin-like peptides play in regulating important life history traits in response to changes in dietary macronutrients.

genetics↗

bioRxiv2024

Cluster Formation and Phase Separation Driven by Mobile Myosin Motors in the Motility Assay

Interactions between F-actin and myosin are critically important for a wide range of biological processes, including cell migration, cytokinesis, and morphogenesis. The motility assay with myosin motors fixed on a surface has been utilized for understanding various phenomena emerging from the interactions between F-actin and myosin. For example, F-actin in the motility assay exhibited distinct collective behaviors when actin concentration was above a critical threshold. Recent studies have performed the myosin motility assay on a lipid bilayer, meaning that myosin motors anchored on the fluid-like membrane have mobility. Interestingly, mobile motors led to very different collective behaviors of F-actin compared to those induced by stationary motors. However, the dynamics and mechanism of the unique collective behaviors have remained elusive. In this study, we employed our cutting-edge computational model to simulate the motility assay with mobile myosin motors. We reproduced the formation of actin clusters observed in experiments and showed that F-actin within clusters exhibits strong polar ordering and leads to phase separation between myosin motors and F-actin. The cluster formation was highly dependent on the average length and concentration of F-actin. Our study provides insights into understanding the collective behaviors of F-actins that could emerge under more physiological conditions.

biophysics↗