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 Wednesday, March 10th in detail:

15:00 - 15:05  Welcome

15:05 - 15:50  Jean-Leon Maitre, Institute Curie, Paris: "Mechanics of human embryo compaction"

Abstract:

During preimplantation development, the mammalian embryo forms the blastocyst which mediates uterine implantation and enables further development of the embryo. In humans, a minority of preimplantation embryos proceed to live birth. As fertility in Europe declines, it becomes increasingly important to understand human embryonic development. Recent studies have characterized the forces shaping the mouse blastocyst but the mechanical properties of the human embryo are unknown. The first morphogenetic movement leading to the formation of the blastocyst is compaction, a process by which cells come into closer contact. Using human embryos donated to research and micropipette aspiration, we measured that tensions at cell surfaces increase during compaction while tensions at cell-cell contacts stay stable. Therefore, mechanical changes associated with compaction are located at the embryo surface, where actomyosin contractility could act. After reducing myosin activity, we find that human embryos decompact and surface tensions are divided by three. Therefore, actomyosin contractility generates the surface tensions driving compaction of the human embryo. Furthermore, we observe that human embryos with impaired compaction fail to grow their surface tension and when blastomeres are excluded from the compacting mass of the embryo, they display lower surface tensions than compacting blastomeres. Together, this study provides the first mechanical measurements of a developing human embryo, the first evidence of the role of actomyosin contractility in shaping the human embryo and mechanistic explanations for defective human embryo morphogenesis. We hope a better understanding of our own development will benefit assisted reproduction technology.

— 10 min break —

16:00 - 16:45  Julie Plastino, Institute Curie, Paris: "Forces drive basement membrane invasion in Caenorhabditis elegans"

Abstract:

Invasion of cells through basement membrane (BM) extracellular matrix barriers is an important process during organ development and cancer metastasis. Much has been understood concerning the cell biology of invasion, but the role of cell mechanics in the invasive process is little studied. During invasion cells breach BM barriers with actin-rich protrusions. It remains unclear, however, if actin polymerization applies pushing forces to help break through BM, or if actin filaments play a passive role as scaffolding for targeting invasive machinery. Here using the developmental event of anchor cell (AC) invasion in Caenorhabditis elegans, we observe that the AC deforms the BM just prior to invasion, exerting forces in the tens of nN range. BM deformation is driven by actin polymerization nucleated by the Arp2/3 complex and its activators, while formins and crosslinkers are dispensable. Delays in invasion upon actin regulator loss are not caused by defects in AC polarity, trafficking or secretion, as appropriate markers are correctly localized in the AC even when actin is reduced and invasion is disrupted. In addition our preliminary results indicate that the AC nucleus is deformed during invasion, and the role played by the nucleus in AC invasion is currently under investigation. Overall cell and nuclear mechanics emerge from this study as important considerations in BM disruption by invading cells.

— 10 min break —

16:55 - 17:40  Allen Ehrlicher, McGill University, Montreal: "YAP mechanosensing in the nucleus"

Abstract:

YAP is a key mechanotransduction protein with essential roles in diverse physiological and pathological processes. Aberrant YAP activity is associated with diverse cancers and oncogenic transcription factors. While several physical interactions have been suggested to regulate YAP translocation between the cytoplasm and nucleus, the principle mechanosensing mechanism has remained unknown. Here we reveal that nuclear-deformation delocalizes lamin A from the nuclear membrane, which uniquely determines YAP localization. In contrast to previous YAP mechanosensing reports, we show that YAP localization is insensitive to cell substrate stiffness or cell spread area, but is dynamic and strongly determined by acto-myosin contractile work that deforms the nucleus. We observe that nuclear deformation causes lamin A to redistribute from the nuclear membrane to the nucleoplasm, and this movement of lamin A enables YAP to enter the nucleus. These results reveal lamin A as a mechanosensitive protein which uniquely determines YAP nuclear localization, and resolve that nuclear deformation is the principle physical stimulus that drives YAP mechanotransduction.