Research at the interface between biophotonics and mechanobiology
Welcome to our research page. Here you can explore how cells respond to physical stimuli such as membrane curvature and mechanical forces. We investigate how optical tweezers can be used to study mechanobiology, including mechanosensing and interactions at the single-molecule level. Read on to learn more about our projects and results.
Mechanosensing by GPCR
In collaboration with the Biomedical Institute at UCPH we investigate how G-protein-coupled receptors (GPCRs) (a major family of cell-surface receptors) respond to mechanical forces. This includes advanced techniques to manipulate and measure forces at the single-molecule level, providing insight into signaling mechanisms. Our research contributes to a deeper understanding of how cells sense and respond to their mechanical environment.
By using optical tweezers or other mechanical tools on cells we apply local or global mechanical stresses to the cells. The biochemical response is monitored using miniGs which bind to GPCRs upon activation.
This work is part of an interdisciplinary consortium called GPCRmec, funded by the Novo Nordisk Foundation, with multiple academic partners.
Membrane curvatures
Membrane curvature plays a crucial role in cellular processes. We investigate how proteins generate and sense or respond to membrane curvature, which is essential for processes such as vesicle formation, cell migration, and filopodia formation. This involves the use of advanced microscopy techniques in parallel with biophysical methods such as optical tweezers to deform membranes into high membrane curvatures.
Review: Emerging Topics in Life sci. (2023) Ruhoff et al.
Review: BioChemical Society Trans. (2023), Ruhoff et al.
Soft Matter (2021) Florentsen et al.
ACS Central Science (2020), Larsen et al.
ACS Nano (2019) Moreno-Pescador
Nature Chemical Biology (2017), Rosholm et al.
Soft Matter (2015), Barooji et al.
Sci. Rep. (2013), Ramesh et al.
Filopodia pulling and twisting dynamics
We discovered a new way that filopodia work. Filopodia are thin, finger-like protrusions that cells use as “feelers” to sense and grab their surroundings. They are found on many cell types and are especially common on moving immune cells and cancer cells where they facilitate invasion.
We found that filopodia can rotate because their inner support structure—made of actin fibers—can twist like a rope. This was the first clear evidence that a bundled set of actin fibers can twist in this way. We also suggested a simple physical explanation for how the twisting happens.
This twisting matters because it can help the cell pull on things it touches—similar to how a twisted rubber band tends to tighten and pull as it relaxes.
- Nature Communications, 2022, Leijnse et al.
- PNAS 2015, Leijnse et al.
- Review in TCB : Ruhoff et al. 2025
- Review in Cytoskeleton 2015 Leijnse et al.
Thermoplasmonics for biology
We have been pioneers in the field of plasmonics in biology. We have quantified and mapped out the optical heating from various nanostructures both theoretically and experimentally. Subsequently, we have used thermoplasmonics—tiny metal structures that can be heated with light—to do very precise manipulation or “microsurgery” on cells or soft materials.
With this method, we can make controlled, local damage to the cell surface or even the membrane around the nucleus (in collaboration with the Cancer Institute). This lets us study how cells sense and repair injuries, which happen often when cells squeeze and move through tissue—especially immune cells and cancer cells.
We also use the same light-based heating tool for bioengineering: for example, to merge (fuse) cell membranes with synthetic membranes, or to locally “switch” membranes into a different physical state in a specific spot (a bit like changing a small patch of butter from solid to soft without affecting the rest).
- Nano Letters Review (2024), Ruhoff et al.
- JOVE (2024), Danielsen et al.
- Nano Letters (2023) Ruhoff et al.
- Nanoscale (2022), Moreno-Pescador et al.
- Chemical Reviews (2019), Jauffred et al.
- ROPP (2017), Bahadori et al.
- Sci. Rep. (2016), Norregaard et al.
- Nano Letters (2015), Rørvig-Lund et al.
- ASC Nano (2010), Bendix et al.
- Nano Letters (2005), Hansen et al.
Single Molecule Biophysics
Using advanced optical trapping (4 trap system from Lumicks) together with microfluidics and confocal imaging, we explore the DNA-protein interactions taking place during replication.
In collaboration with researchers from molecular biology at UCPH we investigate an array of transcription factors and proteins which help organize the genome.
Plant Biophysics
In collaboration with the Staffan Persson Lab (Plant Science, UCPH), Guillermo Pescador (UCPH) and Alexander Rohrbach (Freiburg), we have developed a new label-free microscopy approach that detects intracellular dynamics in plant cells through light scattering. Using this method, we can reveal and quantify previously hidden diffusion dynamics of intracellular vesicles in plant roots.
We also study the biophysics of the plant cell surface using optical trapping and thermoplasmonics as manipulation tools. In particular, we investigate how membrane phase behavior, tension and membrane curvature shape the lateral distribution of proteins.
Cell membrane repair and biophysics of annexins
In collaboration with Jesper Nylandsted at the Danish Research Center we have investigated how cells repair surface lesions by recruiting different types of annexins. We have locally punctures living cells while monitoring recruitment of fluorescent annexins to the site of damage. To gain biophysical insight into the mechanism of annexins we have made in vitro studies using membrane vesicles with encapsulated annexins. these vesicles were optically shape modulated or punctures to understand the reaction of annexins to shape and to formation membrane holes.
Thermoplasmonics is currently being used to study the repair mechanisms of nuclear membranes as well.
- JOVE (2024), Danielsen et al.
- Nanoscale (2022), Moreno-Pescador et al.
- Soft Matter (2021), Florentsen et al.
- J. of Biological Chemistry (2021), Heitmann et al.
- Cells (2020), Bendix et al.
Would you like to learn more about our research? Contact Poul Martin Bendix at bendix@nbi.dk to discuss potential collaborations, or read more about our Publications.