Biology subjects

Kouwer, P. H. J.

Publications and source records attributed to Kouwer, P. H. J..

4 recordsLinked to original sources

bioRxiv2026

Synthetic Fibrous Hydrogels as Minimal Systems to Modulate Cell Migration Modes in 3D

Cell migration in three-dimensional (3D) environments is highly plastic and regulated by extracellular matrix (ECM) cues. Engineered biomaterials provide controllable platforms to investigate how specific matrix signals regulate cell behavior in 3D, yet how defined biochemical signals control migration modes remain unclear. Here, we present tunable fibrous polyisocyanide (PIC) hydrogels functionalized with integrin-binding RGD peptides, cadherin-mimetic HAVDI peptides, or no ligands to direct mesenchymal, hybrid, or amoeboid-like migration of human adipose-derived stem cells without altering matrix mechanics. Using live-cell tracking, 3D displacement microscopy, matrix remodeling analysis, and YAP nuclear localization, we show that ligand identity governs adhesion organization, force transmission, and mechanotransduction. RGD-functionalized matrices promote {beta}1-integrin clustering, extensive matrix remodeling, strong YAP activation and upregulation of migration-related genes. In contrast, non-adhesive matrices limit adhesion formation, resulting in weak force transmission and amoeboid-like behavior. HAVDI-functionalized matrices induce cadherin clustering and heterogeneous cellular responses, indicating that a hybrid migration mode arises from adhesion organization rather than a distinct transcriptional program. Together, these findings demonstrate that ligand identity alone is sufficient to program migration mode in a force-responsive 3D matrix and provide a versatile platform to dissect cell-matrix interactions in complex environments. Statement of significanceO_LICell migration in tissues is highly adaptable, yet precise control of migration modes in defined 3D biomaterials remains challenging. C_LIO_LIWe introduce fibrous PIC hydrogels presenting RGD, HAVDI, or no adhesive ligands to bias human stem cells toward mesenchymal-like, hybrid, or amoeboid-like migration states. C_LIO_LIBy linking ligand identity to adhesion organization, matrix remodeling, YAP mechanotransduction, and gene expression, this work provides a minimal platform to dissect and engineer 3D cell-matrix interactions C_LI

biophysics↗

bioRxiv2024

Deciphering stiffness-driven changes in colorectal cancer by proteomics

Tumor stiffening plays a pivotal role in cancer progression. Increased tumor stiffness, resulting from interactions between cancer cells and their surrounding microenvironment, alters the tumors mechanical properties and significantly impacts cancer growth and metastasis, the primary cause of cancer-related deaths. Despite the importance of tumor stiffness, systematic studies exploring its effect on proteomic profiles are limited. In this study, focused on colorectal cancer, we show that matrix stiffness significantly alters the expression of secreted proteins, while intracellular protein levels remain largely unaffected. Functional assays reveal that the changes in the secretome, driven by matrix stiffness, enhance cell migration, angiogenesis, and matrix remodeling, which collectively contribute to a more aggressive cancer phenotype. Our findings emphasize the critical role of matrix stiffness in driving colorectal cancer progression through changes in the secretome, offering valuable insights for the development of biomechanical cancer therapies. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=140 SRC="FIGDIR/small/618701v1_ufig1.gif" ALT="Figure 1"> View larger version (55K): org.highwire.dtl.DTLVardef@fb6b58org.highwire.dtl.DTLVardef@446a31org.highwire.dtl.DTLVardef@197e22forg.highwire.dtl.DTLVardef@82a896_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2022

Synthetic fibrous hydrogels as a platform to decipher cell-matrix mechanical interactions

The interactions between cells and their direct environment are crucial for cell fate but biochemically and mechanically highly complex, and therefore, poorly understood. Despite recent advances that exposed the impact of a range of different factors, real progress remains challenging, since appropriate controllable matrices and quantitative analysis techniques that cover a range of time and length scales are unavailable. Here, we use a synthetic fibrous hydrogel with nonlinear mechanics to mimic and tailor the bi-directional cell-matrix interactions. Using advanced microscopy-based approaches, we acquire a comprehensive picture of how cellular traction forces, fiber remodeling, matrix stiffening, matrix properties and cellular behavior interact, highlighting for instance, the importance of a fibrous architecture and nonlinear mechanics of the matrix. Complete mapping of cell-matrix interactions at the cellular length scale provides indispensable information for the rational design of biomimetic materials to recreate realistic in vitro cell environments.

biophysics↗

bioRxiv2022

Rapid stem cell spreading induced by high affinity α5β1 integrin-selective bicyclic RGD peptide in biomimetic hydrogels

Cell-matrix interactions form a crucial parameter for the design of a synthetic extracellular matrix (ECM), as they ultimately dictate cell fate and functions. Universally, synthetic biomaterials are conjugated with a linear or cyclic Arg-Gly-Asp (RGD) peptide to establish a direct link of the ECM with the cell. These peptides, however, present low binding affinities and lack selectivity towards integrin subtypes presented on the cell membrane. Here, a highly biomimetic synthetic ECM based on polyisocyanides (PIC) that has been decorated with bicyclic peptides that show a high affinity towards specific integrin subtypes is presented. 3D cell studies show that human adipose-derived stem cells (hASCs) in matrices carrying the optimized bicyclic 5{beta}1 -integrin binder, spread within 24 hours, which is much faster than in other PIC gels, including the default RGD-decorated gel, but also much faster than in the positive Matrigel control. YAP/TAZ staining shows that the rapid morphological change in the 3D microenvironments is YAP independent. The data highlights that the design of synthetic matrices with appropriate, optimized guiding signals is key to guide cells towards a predetermined outcome.

biophysics↗