During morphogenesis, a key process of embryonic development, cells undergo massive rearrangements to give rise to tissue shapes and ultimately organ systems. Shape changes of tissues are naturally driven by forces arising from mechanical interactions between cells and their environment. These forces generate cell movements, mechanical stresses and strains at the tissue level. Abnormalities in these stresses can lead to malformations and developmental disorders, and in mature organisms, cancer can be considered an example of pathological tissue morphogenesis. Knowledge about the forces and stresses generated by cells and tissues is crucial to fully understand embryonic development and related pathological processes. Now, writing in Nature Materials, Maniou et al. 1 present a method to quantify tissue-level morphogenetic forces based on the deformation of three-dimensional soft force sensors …
Dynamic traction force measurements of migrating immune cells in 3D biopolymer matrices
David Böhringer,
Mar Cóndor,
Lars Bischof,
Tina Czerwinski,
Niklas Gampl,
Phuong Anh Ngo,
Andreas Bauer,
Caroline Voskens,
Rocío López-Posadas, et al.
Immune cells, such as natural killer cells, migrate with high speeds of several micrometres per minute through dense tissue. However, the magnitude of the traction forces during this migration is unknown. Here we present a method to measure dynamic traction forces of fast migrating cells in biopolymer matrices from the observed matrix deformations. Our method accounts for the mechanical nonlinearity of the three-dimensional tissue matrix and can be applied to time series of confocal or bright-field image stacks. It allows for precise force reconstruction over a wide range of force magnitudes and object sizes—even when the imaged volume captures only a small part of the matrix deformation field. We demonstrate the broad applicability of our method by measuring forces from around 1 nN for axon growth cones up to around 10 μN for mouse intestinal organoids. We find that natural killer cells show bursts of large traction forces around 50 nN that increase with matrix stiffness. These force bursts are driven by myosin II contractility, mediated by integrin β1 adhesions, focal adhesion kinase and Rho-kinase activity, and occur predominantly when the cells migrate through narrow matrix pores.
Mutation of the ALS-/FTD-Associated RNA-Binding Protein FUS Affects Axonal Development
Francesca W. van Tartwijk,
Lucia C. S. Wunderlich,
Ioanna Mela,
Stanislaw Makarchuk,
Maximilian A. H. Jakobs,
Seema Qamar,
Kristian Franze,
Gabriele S. Kaminski Schierle,
Peter H. St George-Hyslop, et al.
The Journal of Neuroscience: The Official Journal of the Society for Neuroscience
44
(27)
e2148232024
(2024)
| Journal
Aberrant condensation and localization of the RNA-binding protein (RBP) fused in sarcoma (FUS) occur in variants of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Changes in RBP function are commonly associated with changes in axonal cytoskeletal organization and branching in neurodevelopmental disorders. Here, we asked whether branching defects also occur in vivo in a model of FUS-associated disease. We use two reported Xenopus models of ALS/FTD (of either sex), the ALS-associated mutant FUS(P525L) and a mimic of hypomethylated FUS, FUS(16R). Both mutants strongly reduced axonal complexity in vivo. We also observed an axon looping defect for FUS(P525L) in the target area, which presumably arises due to errors in stop cue signaling. To assess whether the loss of axon complexity also had a cue-independent component, we assessed axonal cytoskeletal integrity in vitro. Using a novel combination of fluorescence and atomic force microscopy, we found that mutant FUS reduced actin density in the growth cone, altering its mechanical properties. Therefore, FUS mutants may induce defects during early axonal development.
Mechanics in the nervous system: From development to disease
Physical forces are ubiquitous in biological processes across scales and diverse contexts. This review highlights the significance of mechanical forces in nervous system development, homeostasis, and disease. We provide an overview of mechanical signals present in the nervous system and delve into mechanotransduction mechanisms translating these mechanical cues into biochemical signals. During development, mechanical cues regulate a plethora of processes, including cell proliferation, differentiation, migration, network formation, and cortex folding. Forces then continue exerting their influence on physiological processes, such as neuronal activity, glial cell function, and the interplay between these different cell types. Notably, changes in tissue mechanics manifest in neurodegenerative diseases and brain tumors, potentially offering new diagnostic and therapeutic target opportunities. Understanding the role of cellular forces and tissue mechanics in nervous system physiology and pathology adds a new facet to neurobiology, shedding new light on many processes that remain incompletely understood.
Tensed axons are on fire
Kristian Franze
Proceedings of the National Academy of Sciences of the United States of America
121
(5)
e2321811121
(2024)
| Journal
| PDF
Kontakt
Abteilung Neuronale Mechanik Prof. Kristian Franze Principal Investigator
Max-Planck-Zentrum für Physik und Medizin Kussmaulallee 2 91054 Erlangen
