Pericytes, the mural cells of blood microvessels, are important regulators of vascular morphogenesis and function that have been postulated to mechanically control microvascular diameter through as yet unknown mechanisms.

The aim of this thesis is to study cell-cell interactions and the development of an assay to explore and quantify the exchange of membrane compounds.

Chemical-induced organ toxicity is a major concern in the development and use of chemicals, including drugs, pesticides, industrial chemicals and cosmetics. In the last decades, the onset and progression of chemical-induced organ toxicity has been linked amongst others to perturbation of mitochondri…

Synthetic hydrogels that mimic the natural extracellular matrix in the biophysical and biochemical cues it provides to cells are in high demand, however the cell phenotypes as they are observed in vivo in numerous cases have yet to be attained.

This thesis aims to test in vitro pipelines to rapidly and cost-effectively identify molecular mechanisms that drive adverse outcomes in clinical use.

Mechanical forces are known to play an important role in bacterial colonies. In this dissertation, we study the self-organization at various stages of growing bacterial colonies, and focus on the mechanical effects of cell growth.

During the development of the (human) body from a single fertilized egg, organs and structures must form. The development and growth of biological forms is called morphogenesis.

Despite being the object of intense study, embryonic development has been difficult to model due to a number of reasons. First, complex tissues can be comprised of many cell types, of which we probably only know a subset.

Promotor: R. Tijdeman, Co-promotor: C. Kraaikamp

Promotor: B. van de Water

Parkinson's disease is the second most common neurodegenerative disease in the world. One of its symptoms is the loss of dopaminergic neurons in the substantia nigra pars compacta.

Promotor: B.van de Water, Co-promotor: L.S.Price

In this thesis, we describe the potential of cell mechanical phenotyping for immune cell characterization, diagnosis, drug testing, as well as treatment of disease.

In this thesis, single-cell approaches were applied to characterize the impact of aging on the immunological B cell landscape in different models of atherosclerotic cardiovascular disease, with the goal to identify and study new B cell-associated biomarkers and therapeutic targets to halt atherosclerosis…

Mechanical interactions between cells and their environment play an important role in many biological processes.

Promotor: Prof.dr. J. Kuiper

Promotor: P. J. J. Hooykaas, Co-promotor: R. Offringa

Drug induced organ toxicity is the main problem of the drug development and drug usage in the clinic. The liver and kidneys are the most sensitive organs towards drug induced toxicity.

Promotor: Prof.dr. J. Kuiper

The aim of this thesis was to study phage infection in Streptomyces, focused on cell wall-deficient cells. Bacteriophages (or phages in short) attach to the cell wall of bacteria after which they replicate and lyse the host cell.

Cardiovascular disease is a major global burden and atherosclerosis is the main underlying pathological process.

Cell-based medicinal products (CBMPs), such as CAR T cells, are highly complex biopharmaceutical products offering various treatment options for serious illnesses such as cancer or autoimmune diseases.

Gaucher disease is a rare metabolic disorder, in which a mutation of the enzyme glucocerebrosidase (GBA1) causes buildup of its substrate glucosylceramide and the deacylated counterpart glucosylsphingosine in lysosomes.

Epithelial-mesenchymal plasticity (EMP) and tumor cell migration play an important role in cancer progression, and an improved understanding of the mechanisms underlying these concepts is essential for developing new targeted approaches.

Bacteria have the ability to alter their morphology in order to adapt to changing environments.

There is a need for alternative methods to replace, reduce and refine (3R) animal experimentation. Combining experimental data from high-throughput in vitro studies with in silico modeling is a promising approach to unravel the effect of chemicals on living cells and to gain a better understanding of…

This work describes the use of click-to-release chemistry to get spatiotemporal control over immunocytokine activity. Until now, immunocytokines (cytokines coupled to a tumor-targeting-moiety) remained active throughout the body, being able to bind their respective receptors, causing mild to severe…

Promotores: Prof.dr. G.F.A. Kersten, W. Jiskoot, Co-promotor: J-P. Amorij

This thesis advances our understanding of lipid uptake, a vital first step in lipid metabolism, by developing innovative click chemistry-based tools to study how immune cells internalize lipids.

A new type of tripodal squaramide-based supramolecular hydrogels is developed and studied.

During embryonic growth, cells proliferate, differentiate, and collectively migrate to form different tissues at the right position and time in the body.

Almost all bacteria are enveloped by a cell wall that provides cellular protection.

Aspergillus niger is an important industrial producer of organic acids and enzymes producing large amounts of spent fungal biomass.

This dissertation aims to advance understanding of amoeboid single cell migration under the influence of changing physicochemical environmental properties. The particular focus is on the relatively unknown influence of differing physical properties in the extracellular environment, such as the migratory…

Traditional drug discovery approaches have been hampered by (in vitro) cell-culture models that poorly represent the situation in the human body.

Acute cardiovascular syndromes, including myocardial infarction or stroke, are the principal cause of death in the Western society. The main underlying pathology of cardiovascular diseases is atherosclerosis, which is caused by the accumulation of lipids and inflammatory cells in the vessel wall, in…

In this research project, we aimed to obtain more insight in the role of mast cells in the immune driven disorders rheumatoid arthritis and atherosclerosis.

In this thesis, we have studied cell images from two types of cells, including pollen grains and the immune cells, neutrophils. These images are captured using a bright field microscope and a confocal microscope.

This thesis focuses on two processes involved in fighting infections: metabolism and immune cell motility and navigation.

There is an urgent need for more physiologically relevant cell culture methods to guide compound selection in pre-clinical stages of the drug development pipeline.

Promotor: T. Schmidt, Co-promotor: S. J.T. van Noort

Promotor: M. Danhof Co-promotor: O.E. Della Pasqua

The bacterial cell wall is a nearly universal structure that offers protection and gives the cell its shape. However, environmental stressors, such as cell wall-targeting antibiotics and hyperosmotic conditions, can induce bacteria to shift to a wall-deficient state. It is unknown whether the lack of…

CONCLUSION: This study demonstrates that human macrophages can be induced to exert direct anti-tumor activity against osteosarcoma cells. Our observation that the induction of macrophage anti-tumor activity by L-MTP-PE required IFN-gamma may be of relevance for the optimization of L-MTP-PE therapy in…

This dissertation contains four works during my PhD. Different biomaterials have been designed based on coiled-coil peptides. These biomaterials have a range of applications, inclusing drug delivery, cell sorting to cell-cell fusion.

We have studied the impact of particle shape anisotropy, multivalent interactions and flexibility on systems of micron-sized colloidal particles.

This thesis describes the design and synthesis of fragments of various cell wall carbohydrates of the Streptococcus species, including the branched Group B-specific antigen (GBC) of Group B Streptococcus, glycerol phosphate (GroP) modified group A carbohydrate (GAC), and the O-acetylated type 1 capsular…

This thesis examines strategies to address the global threat of antimicrobial resistance (AMR). Antimicrobial resistance poses an increasing global health risk, highlighting the need for new treatments against Gram-negative pathogens.

In order to gain a better insight into the basis of the rapid jasmonic acid (JA)-mediated stress response, an integrated approach using a targeted high-resolution mass spectrometry-based (HRMS) platform, was conducted to monitor the metabolism of JA using the model system of cell suspension cultures…