Biomedicines and Cellular Biomechanics

Cardiovascular diseases remain the leading cause of death worldwide, underscoring the urgent need to deepen our understanding of vascular biology in health and disease. The human vasculature is a complex network of arteries, veins, and capillaries forming specialised vascular beds across organs, composed of diverse cell types that maintain vessel integrity and function.

Our group focuses on endothelial cells, the specialised cells lining all blood vessels. Positioned at the interface between blood and vessel wall, endothelial cells constantly experience mechanical forces such as shear stress, cyclic stretch, and tension from the extracellular matrix. These biomechanical cues are crucial for vascular homeostasis and adaptive responses.

At the molecular level, endothelial function is tightly regulated by BMP/TGFβ signalling pathways, which integrate extracellular signals via canonical Smad-dependent and non-Smad mechanisms. Dysregulation of these pathways is linked to rare genetic vascular disorders like pulmonary arterial hypertension (PAH) and hereditary haemorrhagic telangiectasia (HHT), as well as common vascular diseases such as atherosclerosis.

Our goal is to unravel how biochemical and biomechanical signals converge on BMP/TGFβ and related pathways in endothelial cells, to uncover mechanisms underlying vascular pathobiology relevant to both rare and common cardiovascular diseases.

To achieve this, we employ advanced cell biology techniques using human vascular cells, including iPSC-derived endothelial cells, alongside innovative devices that enable precise mechanical stimulation in vitro. This approach models vascular disease under physiologically relevant conditions while adhering to the 3Rs principles (Replacement, Reduction, Refinement). Through this interdisciplinary strategy, our workgroup strives to advance mechanistic insights into vascular signalling and contribute to the development of novel therapeutic strategies for cardiovascular diseases. We achieve this by multiple cooperations with our scientific partners. 

ACVRL1 mutation and Cell Mechanics in Endothelial cells for Hereditary Haemorrhagic Telangiectasia/ Morbus Osler

In this project, we aim to elucidate the role of biomechanics in HHT. To achieve this, we utilise iPSCs with heterozygous ACVRL1 mutation (encoding ALK1) and differentiate them into endothelial cells (iECs). We focus on both iEC adaptation to mechanical stressors as well as pulling forces during actin-driven filopodia formation in sprouting angiogenesis (Hiepen, C., Benamar, M. et al. 2025, Communications biology). Alterations in cellular biomechanics are assessed using various methods, including integration of optical force-sensors and Traction Force Microscopy. 

Arteriovenous Malformation ON a CHIP platform

We developed a microfluidic device recapitulating typical cerebral arteriovenous malformation (AVM) geometries to investigate endothelial responses to real haemodynamic shear forces and complex flow patterns within disease-relevant vascular geometries. Our current focus is to further equip these Vasc-on-Chip platforms with sensor systems to report on barrier functionality as well as diversifying the vessel types to be printed.

VASCular endothelial cell STRETCH device for junctional integrity studies

Maintaining the integrity of endothelial cell junctions is essential for vascular barrier function, and potential disruptions in these junctions might contribute to the pathophysiology of hereditary haemorrhagic telangiectasia (HHT) and other vascular diseases. To better understand how mechanical forces influence junctional stability in both healthy and diseased endothelial cells, we are developing a micro-scale stretching device that mimics the dynamic environment of blood vessels and challenges junctional integrity.

Group Leader: Christian Hiepen

Research Assistant: Marcel Gorka

Chris Hiepen is a trained molecular biologist, with expertise in biochemistry, regenerative therapies and cell biology. During his doctoral and postdoctoral studies in the group of Petra Knaus at FU Berlin and Charité Berlin, he developed a keen interest in the role of BMP/TGFβ signalling in endothelial cells, the role of non-Smad signalling pathways and the cellular cytoskeleton as well as cellular biomechanics at the cell-to-ECM interface. After this Chris co-developed digital resources for induced pluripotent Stem Cells (iPSCs) at the Fraunhofer Institute for Biomedical Engineering IBMT. Chris was appointed in 2024 full professor at the Westphalian University of Applied Sciences. Since then, he has been building his interdisciplinary research group with a focus on unsolved biomedical questions and the role of cellular biomechanics using iPSCs.

We offer a laboratory practical course (Laborpraxis LAB(M)) once per year for interested students who want to gain hands-on experience in tissue culture techniques. Additionally, voluntary semester-long research assistant positions are available (starting from 5th semester) upon request (successful course participation in ZKT and BMT are compulsory). 

The bachelor’s module "Biomaterials and Tissue Engineering" (BMT)” of the bachelor’s program provides initial insights into our research areas and offers students the opportunity to actively participate in prototype design.

If you are interested in thesis projects such as Bachelor’s or Master’s theses, please contact Prof. Hiepen directly by email.