Biology subjects

van Erp, M.

Publications and source records attributed to van Erp, M..

5 recordsLinked to original sources

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↗

bioRxiv2021

Cornering an Ever-Evolving Coronavirus: TATX-03, a fully human synergistic multi-antibody cocktail targeting the SARS-CoV-2 Spike Protein with in vivo efficacy

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created an ongoing global human health crisis and will likely become endemic, requiring novel sustainable therapeutic strategies. We report on the discovery of a fully human multi-antibody cocktail (TATX-03) targeting diversified non-overlapping epitopes on the SARS-CoV-2 spike protein that suppressed replication-competent viral titers to undetectable levels in the lungs of SARS-CoV-2 challenged hamsters upon both prophylactic and therapeutic administration. While monotherapy with two of the individual cocktail components also showed clear in vivo protection, neither recapitulated the efficacy of TATX-03. This synergistic effect was further supported by examining in vivo efficacy of these individual antibodies and corresponding combination therapy at a lower dose. Furthermore, in vitro screenings using VSV-particles pseudo-typed with spike proteins representing the SARS-CoV-2 variants of concern Alpha, Beta, and Delta showed that TATX-03 maintained its neutralization potency. These results merit further development of TATX-03 as a potential therapy for SARS-CoV-2 infection with resistance to mutagenic escape.

immunology↗

bioRxiv2021

Functional basis for calmodulation of the TRPV5 calcium channel

Within the transient receptor potential (TRP) superfamily of ion channels, TRPV5 is a highly Ca2+-selective channel important for active reabsorption of Ca2+ in the kidney. Its channel activity is controlled by a negative feedback mechanism involving calmodulin (CaM) binding. Combining advanced microscopy techniques and biochemical assays, this study characterized the dynamic bilobal CaM regulation and binding stoichiometry. We demonstrate for the first time that functional (full-length) TRPV5 interacts with CaM in the absence of Ca2+, and this interaction is intensified at increasing Ca2+ concentrations sensed by the CaM C-lobe that achieves channel pore blocking. Channel inactivation occurs without CaM N-lobe calcification. Moreover, we reveal a 1:2 stoichiometry of TRPV5:CaM binding by implementing single molecule photobleaching counting, a technique with great potential for studying TRP channel regulation. In conclusion, our study proposes a new model for CaM- dependent regulation - calmodulation - of the Ca2+-selective TRPV5 that involves apoCaM interaction and lobe-specific actions.

cell biology↗

bioRxiv2020

An Organoid for woven Bone

Bone formation (osteogenesis) is a complex process in which cellular differentiation and the generation of a mineralized organic matrix are synchronized to produce a hybrid hierarchical architecture. To study the mechanisms of osteogenesis in health and disease, there is a great need for functional model systems that capture in parallel both cellular and matrix formation processes. Stem cell-based organoids are promising as functional, self-organizing 3D in vitro models for studying the physiology and pathology of various tissues. However, for human bone, no such functional model system is yet available. This study reports the in vitro differentiation of human bone marrow stromal cells into a functional 3D self-organizing co-culture of osteoblasts and osteocytes, creating an organoid for early stage bone (woven bone) formation. It demonstrates the formation of an organoid where osteocytes are embedded within the collagen matrix that is produced by the osteoblasts and mineralized under biological control. Alike in vivo osteocytes the embedded osteocytes show network formation and communication via expression of sclerostin. The current system forms the most complete 3D living in vitro model system to investigate osteogenesis, both in physiological and pathological situations, as well as under influence of external triggers (mechanical stimulation, drug administration).

bioengineering↗

bioRxiv2019

Community Standards for Open Cell Migration Data

Cell migration research has become a high-content field. However, the quantitative information encapsulated in these complex and high-dimensional datasets is not fully exploited due to the diversity of experimental protocols and non-standardised output formats. In addition, typically the datasets are not open for reuse. Making the data open and Findable, Accessible, Interoperable, and Reusable (FAIR) will enable meta-analysis, data integration, and data mining. Standardised data formats and controlled vocabularies are essential for building a suitable infrastructure for that purpose but are not available in the cell migration domain. We here present standardisation efforts by the Cell Migration Standardisation Organization, CMSO, an open community-driven organisation to facilitate the development of standards for cell migration data. This work will foster the development of improved algorithms and tools, and enable secondary analysis of public datasets, ultimately unlocking new knowledge of the complex biological process of cell migration.

bioinformatics↗