We investigate how cellular forces, local cell, and tissue viscoelasticity, and cellular mechanosensitivity contribute to CNS development and disease. Methods we are exploiting include atomic force microscopy, traction force microscopy, custom-built simple and complex compliant cell culture substrates, optical microscopy including confocal laser scanning microscopy, and cell biological techniques.
- Role of tissue mechanics in regulating neuronal development
- Quantification of CNS tissue mechanics in health and disease
- Role of tissue mechanics in pathological processes such as foreign body reactions and spinal cord injuries
- Symmetry breaking of microtubule networks in neurons
- Development of atomic force microscopy-based methods to measure and manipulate tissue mechanics
- Development of AI-based software for automated data/image analysis
How neural stem cells shape their regulatory environment in the adult CNS
(FAU Funds)Term: 1. June 2023 - 30. November 2025
Funding source: Mittelgeber / Förderprogramme
An adverse local environment ("niche") impairs the activity of neural stem cells (NSCs) in the adult brain. We investigate the new hypothesis that NSCs play an active role in generating favorable and adverse niche conditions. Specifically, we will investigate how dysfunctional NSCs generate adverse niche conditions focusing i) on the composition and the biomechanical properties of the extracellular matrix and ii) on NSC-derived exosomes and their composition.
Exploring Brain Mechanics (EBM): Understanding, engineering and exploiting mechanical properties and signals in central nervous system development, physiology and pathology
(Third Party Funds Group – Overall project)Term: 1. January 2023 - 31. December 2026
Funding source: DFG / Sonderforschungsbereich / Transregio (SFB / TRR)
Thecentral nervous system (CNS) is our most complex organ system. Despite tremendousprogress in our understanding of the biochemical, electrical, and geneticregulation of CNS functioning and malfunctioning, many fundamental processesand diseases are still not fully understood. For example, axon growth patterns inthe developing brain can currently not be well-predicted based solely on thechemical landscape that neurons encounter, several CNS-related diseases cannotbe precisely diagnosed in living patients, and neuronal regeneration can stillnot be promoted after spinal cord injuries.
Duringmany developmental and pathological processes, neurons and glial cells aremotile. Fundamentally, motion is drivenby forces. Hence, CNS cells mechanicallyinteract with their surrounding tissue. They adhere to neighbouring cells and extracellular matrix using celladhesion molecules, which provide friction, and generate forces usingcytoskeletal proteins. These forces aretransmitted to the outside world not only to locomote but also to probe themechanical properties of the environment, which has a long overseen huge impacton cell function.
Onlyrecently, groups of several project leaders in this consortium, and a few other groupsworldwide, have discovered an important contribution of mechanical signalsto regulating CNS cell function. For example, they showed that brain tissuemechanics instructs axon growth and pathfinding in vivo, that mechanicalforces play an important role for cortical folding in the developing humanbrain, that the lack of remyelination in the aged brain is due to an increasein brain stiffness in vivo, and that many neurodegenerative diseases areaccompanied by changes in brain and spinal cord mechanics. These first insights strongly suggest thatmechanics contributes to many other aspects of CNS functioning, and it islikely that chemical and mechanical signals intensely interact at the cellularand tissue levels to regulate many diverse cellular processes.
The CRC 1540 EBM synergises the expertise of engineers, physicists,biologists, medical researchers, and clinicians in Erlangen to explore mechanicsas an important yet missing puzzle stone in our understanding of CNSdevelopment, homeostasis, and pathology. Our strongly multidisciplinary teamwith unique expertise in CNS mechanics integrates advanced invivo, in vitro, and in silico techniques across time(development, ageing, injury/disease) and length (cell, tissue, organ) scalesto uncover how mechanical forces and mechanical cell and tissue properties,such as stiffness and viscosity, affect CNS function. We especially focus on(A) cerebral, (B) spinal, and (C) cellular mechanics. Invivo and in vitro studies provide a basic understanding ofmechanics-regulated biological and biomedical processes in different regions ofthe CNS. In addition, they help identify key mechano-chemical factors forinclusion in in silico models and provide data for model calibration andvalidation. In silico models, in turn, allow us to test hypotheses without the need of excessive or even inaccessibleexperiments. In addition, they enable the transfer and comparison of mechanics data and findingsacross species and scales. They also empower us to optimise processparameters for the development of in vitro brain tissue-like matricesand in vivo manipulation of mechanical signals, and, eventually, pavethe way for personalised clinical predictions.
Insummary, we exploit mechanics-based approaches to advance ourunderstanding of CNS function and to provide the foundation for futureimprovement of diagnosis and treatment of neurological disorders.
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