Biology subjects

Oosterwijk, E.

Publications and source records attributed to Oosterwijk, E..

3 recordsLinked to original sources

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

Intravesical BCG in patients with non-muscle invasive bladder cancer induces trained immunity and decreases respiratory infections

Bacillus Calmette-Guerin (BCG) is recommended as intravesical immunotherapy to reduce the risk of tumor recurrence in patients with non-muscle invasive bladder cancer (NMIBC). Currently, it is unknown whether intravesical BCG application induces trained immunity. Here, we found that intravesical BCG does induce trained immunity based on an increased production of TNF and IL-1{beta} after heterologous ex-vivo stimulation of circulating monocytes 6- 12 weeks after intravesical BCG treatment; and a 37% decreased risk (OR 0.63 (95% CI 0.40- 1.01)) for respiratory infections in BCG-treated versus non-BCG-treated NMIBC patients. An epigenomics approach combining ChIP-sequencing and RNA-sequencing with in-vitro trained immunity experiments identified enhanced inflammasome activity in BCG-treated individuals. Finally, germline variation in genes that affect trained immunity was associated with recurrence and progression after BCG therapy in NMIBC, suggesting a link between trained immunity and oncological outcome.

immunology↗

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↗