Pressure, density, elasticity are classical physical properties, which are required to fully describe the processes in human cell assemblies – for example, to distinguish tumours from healthy tissue or to stimulate the regrowth of nerve cells. These examples illustrate how physics can provide new stimuli for basic medical research.

Today, modern physical methods and physical thinking are being transferred towards physiological application worldwide. In order to promote the exchange between different researchers and working groups, the Max Planck Zentrum für Physik und Medizin is starting a new series of public mini-symposia, in which two to three scientists from North America, Europe or Asia will present their work virtually. The series starts on March 10th, with further symposia planned for March 11th and 19th — and more to follow…

To take part in the symposia, please register for MPL's scientific lectures newsletter (please ensure that you tick the "scientific lecture" checkbox). We will send the Zoom links about one hour before the symposium starts.

The schedule for Tuesday, March 30th in detail:

15:00 - 15:05  Welcome

15:05 - 15:50  Lukas Kapitein, Utrecht University: "Super-resolution microscopy of cellular architecture in health and disease"

Abstract:

Our group aims to understand how specialized cells, such as neurons and epithelial cells, establish their shape and intracellular organization and how these mechanisms are altered in pathological conditions. The cytoskeleton and its associated motor proteins play an important role in cellular organization and dynamics, because they control mechanical properties of cells, establish long-range order within cells, and drive the subcellular patterning of organelles. To explore these important processes, we combine innovative intracellular assays with advanced high-resolution microscopy. In this presentation, I will first highlight how these approaches have helped us to reveal a key architectural principle of the neuronal microtubule cytoskeleton that explains how different motor proteins can selectively transport cargoes to either axons or dendrites. In addition, I will demonstrate how we are currently using similar approaches to understand how the coronavirus SARS-CoV-2 alters the morphology of human airway cells.

— 10 min break —

16:00 - 16:45  Louise Jawerth, University Leiden: "Blood coagulation and protein condensation: physics of important biological material"

Abstract:

Throughout my scientific career, I have sought to uncover the physical principles that govern how microscopic processes give rise to complex biological phenomena, with a focus on understanding prominent biological functions as well as their dysfunction in disease. As an experimentalist, my approach has often relied on building novel tools to quantitatively measure the properties of biological materials while simultaneously advancing the field of soft condensed matter physics to establish the necessary conceptual framework. In this talk, I will describe this approach on two important biological phenomena. In the first part, I will discuss our work in understanding the physics of blood clots, which are important for wound healing but can also cause cardiovascular diseases. We investigated the unusual, non-linear material properties of the biopolymer network fibrin that comprises the structural scaffold of blood clots. Using atomic force microscopy, bulk rheology, image processing and other tools in novel ways, I directly measured the properties of fibrin networks on various length scales. We uncovered that the mechanical behavior of a fibrin network arises from the architecture of the network in an unexpected, emergent way. From this, we also elucidated the role of small, contractile cells - called platelets - that alter the material properties of fibrin as well as more complex blood clots. In the second part, I will discuss our work in understanding droplets of proteins that condense out of solution to form distinct liquid-like phases inside of cells. Such protein condensation has been recently identified in myriad important biological phenomena. Although the liquid-like nature of these protein droplets is one of their defining characteristics, most work has only been observational and measuring their properties quantitatively is one of the big challenges in the field. In this part of the talk, I will discuss our advances to quantify the properties of this novel class of soft materials using optical tweezers and optical microscopy-based methods. To begin, I will describe the transition of liquid protein condensates into harmful fibers associated with neurodegenerative diseases, such as ALS. Then, I will discuss a common feature of protein condensates in which they age into predominantly elastic materials (distinct from fiber formation). We find this slow evolution of the material properties exhibits similarities to the aging observed in traditional glasses. Lastly, I will motivate why I believe that the study of protein condensation will be one of the most important areas of contemporary soft condensed matter physics and why creating such an understanding will be critical for diagnosing and curing many diseases.

— 10 min break —

16:55 - 17:40  Moritz Kreysing, Max Planck Institute of Molecular Cell Biology and Genetics, Dresden: "Controlling the Physics of Cellular Organization"

Abstract:

Imagine light microscopy became interactive like a computer game.

Rather than observing the miracles of cell biology hands tied, we’d be in control of the spatial dynamics and transformations that govern cellular organization and embryogenesis. We would understand how the cellular constituents feel like, how their material properties change under drug treatments, and how re-arrangements of chromatin impact cell identity. We were to provoke medically relevant phenotypes for research without changing cellular biochemistry, and we would assist early human development in reproduction clinics far beyond todays capabilities.

Towards this end, my lab pioneered the optical control of cytoplasmic motion, which we refer to as Focused-Light-Induced-Cytoplasmic-Streaming (FLUCS). Using FLUCS, we successfully gained interactive control of central developmental programs such as body axis formation in the C. elegans embryo. For example, our research established that cytoplasmic flows localize PAR proteins. This polarization process can be accelerated, spatially modulated, and even fully reversed via FLUCS leading to conclusive phenotypes downstream (Mittasch et al 2018, Kreysing 2019). Similarly, on the supra-molecular level, we recently succeeded to control phase-separation in space and time (in preparation). As a non-invasive method, FLUCS furthermore enables to measure material properties, even through cell walls, while circumventing conceptual and technical problems of classic methods. Such rheological measurements can inform about the metabolic state of cells (Mittasch et al 2018) and permit to dissect functional material properties of organelles with respect to the underlying biochemical pathways and/or drug treatment (Mittasch et al, 2020). Recently, we found that FLUCS can successfully be applied also inside the cell nucleus. This finding motivates us to refine FLUCS for sub-diffraction micro-manipulations. These will enable the induction of medically relevant phenotypes for cancer and developmental research. Furthermore, the non-invasive re-positioning of chromosomes might serve as a possible basis to assist earliest human development after in-vitro fertilization, such as to help the correct segregation of chromosomes to avoid human aneuploidies and developmental defects.

The ability to move chromatin inside living cells will furthermore help us to understand the biophysical mechanisms that promote retinal transparency (Solovei et al, 2009, Kreysing et al 2012, Subramanian et al 2019). This also constitutes the starting point of our EU funded project to make living tissues transparent by genetics (Subramanian et al, 2020) in order to facilitate high resolution microscopy of biological processes in their native in vivo contexts.