Biology subjects

Essmann, C. L.

Publications and source records attributed to Essmann, C. L..

3 recordsLinked to original sources

bioRxiv2026

Fibroblast-derived Collagen VI shapes the structure and function of the tumor-immune microenvironment in clear cell renal cell carcinoma

The importance of the extracellular matrix (ECM) influencing tumor biology in stroma-rich tumors is well established. However, the relevance of individual ECM proteins in rather stroma-poor cancers such as clear cell renal cell carcinoma (ccRCC) is ill-defined. Using bulk proteomics, spatial imaging, and single-cell transcriptomics, we identify collagen VI (COL6) as a predominant ECM component of the ccRCC interstitial stroma, synthesized primarily by fibroblasts and pericytes. Using cell-derived matrix (CDM) models, we demonstrate that COL6 is essential for maintaining an isotropic ECM network architecture and governs the broader matrisomal composition, with direct pro-proliferative consequences for tumor cells both in vitro and in situ. Granular spatial analysis reveals that COL6-rich stromal septa constrain tumor-infiltrating T cells to boundary zones, where CD8+PD1+ phenotypes predominate. Importantly, tyrosine kinase inhibition (TKI) with cabozantinib suppresses COL6 expression in fibroblasts in vitro and in ex vivo tumor models, mirroring COL6-depleted CDM phenotypes. Our findings establish COL6 as a central stromal regulator of ccRCC tumor biology and immune contexture, revealing ECM remodeling as an underappreciated mechanism of TKI action, with implications for combination immunotherapy strategies.

cancer biology↗

bioRxiv2023

The influence of internal pressure and neuromuscular agents on C. elegans biomechanics: an empirical and multi-compartmental in silico modelling study

The function of a specific tissue and its biomechanics are interdepended, with pathologies or ageing often being intertwined with structural decline. The biomechanics of Caenorhabditis elegans (C. elegans), a model organism widely used in pharmacological and ageing research, has been established as biomarker for healthy ageing, though the mechanics of individual tissues have remained elusive. In this study we investigated the biomechanics of healthy C. elegans cuticle, muscle tissue, and pseudocoelom using a combination of indentation experiments and in silico modelling. Nematode stiffness measurements were performed using an atomic force microscope. The worms cylindrical body was approximated using a novel three-compartmental nonlinear finite element model, enabling analysis of how changes in the elasticity of individual compartments affect the bulk stiffness of C. elegans. The parameters of the model were then fine-tuned to match the simulation force-indentation output to the experimental data. To test the finite element model, distinct compartments were modified experimentally. Our in silico results, in agreement with previous studies, suggest that hyperosmotic shock reduced stiffness by decreasing the C. elegans internal pressure. Unexpectedly, treatment with the neuromuscular agent aldicarb, traditionally associated with muscle contraction, reduced stiffness by decreasing the internal pressure. It challenges previous assumptions about the effects of aldicarb. Furthermore, our finite element model can offer insights into how drugs, mutations or processes like ageing target individual tissues.

bioengineering↗

bioRxiv2021

Meisosomes, folded membrane platforms, link the epidermis to the cuticle in C. elegans

Apical extracellular matrices (aECMs) form a physical barrier to the environment. In C. elegans, the epidermal aECM, the cuticle, is composed mainly of different types of collagen, associated in circumferential ridges separated by furrows. Here, we show that in mutants lacking furrows, the normal intimate connection between the epidermis and the cuticle is lost, specifically at the lateral epidermis, where, in contrast to the dorsal and ventral epidermis, there are no hemidesmosomes. At the ultrastructural level, there is a profound alteration of structures that we term "meisosomes", in reference to eisosomes in yeast. We show that meisosomes are composed of stacked parallel folds of the epidermal plasma membrane, alternately filled with cuticle. We propose that just as hemidesmosomes connect the dorsal and ventral epidermis, above the muscles, to the cuticle, meisosomes connect the lateral epidermis to it. Moreover, furrow mutants present marked modifications of the biomechanical properties of their skin and exhibit a constitutive damage response in the epidermis. As meisosomes co-localise to macrodomains enriched in phosphatidylinositol (4,5) bisphosphate, they might act, like eisosomes, as signalling platforms, to relay tensile information from the aECM to the underlying epidermis, as part of an integrated stress response to damage.

cell biology↗