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.
My research focuses on experimental and computational soft tissue biomechanics with special emphasis on human brain mechanics and the relationship between brain structure and function. In addition, we study the mechanics of hydrogels with the aim to identify substitutes for native human tissues with similar mechanical properties for applications in tissue engineering and biofabrication.
Research projects
Mechanics-augmented brain surgery
(Third Party Funds Single)
Term: 1. October 2024 - 30. September 2029
Acronym: MAGERY
Funding source: ERC Starting Grant
URL: https://www.lkm.tf.fau.eu/
This project aims at revolutionising the treatment of brain disorders through mechanics-augmented brain surgery (MAGERY). Due to the ultrasoft nature of brain tissue, surgical procedures have exceptionally high requirements for minimal invasiveness and maximal safety. During the procedure, brain tissue largely deforms and is easily loaded beyond its functional tolerance. A promising technology to improve surgical outcomes is to integrate virtual information either through immersed virtual reality (VR) in training and planning or through augmented reality (AR) overlaying virtual information with the surgeon’s real view. Despite rapid advances, to date, most VR/AR solutions have disregarded the complex region-dependent mechanical properties of brain tissue and mechanics-induced cell dysfunction or death.
The MAGERY project will follow a new paradigm by focusing on brain mechanics. We imply that we can minimise unnecessary brain tissue damage by integrating continuum mechanics-based simulations into VR/AR solutions. Realising this objective will require to combine state-of-the-art approaches in live cell imaging, nonlinear continuum mechanics, and computational engineering. The applicant and the MAGERY team will for the first time perform simultaneous large-strain mechanical measurements and multiphoton microscopy, and, through modelling and simulations, identify thresholds for tissue and cell damage under complex three-dimensional loadings. By merging simulation results and VR/AR techniques, this project strives towards real-time predictions of brain tissue deformation and corresponding damage. With her pioneering role in testing and modelling the complex behaviour of human brain tissue, the applicant has excellent prerequisites to tackle these challenges.
If successful, this project can not only revolutionise VR/AR for brain surgery, but also leverage our understanding of the cellular response to three-dimensional mechanical loading across length and time scales.
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
Acronym: SFB 1540 - EBM
Funding source: DFG / Sonderforschungsbereich / Transregio (SFB / TRR)
URL: https://www.crc1540-ebm.research.fau.eu/
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.
Modellierung und Simulation der Regeneration von Rückenmarksgewebe (B01)
(Third Party Funds Group – Sub project)
Project leader: Silvia Budday, Paul Steinmann
Term: 1. January 2023 - 31. December 2026
Acronym: SFB 1540 B01
Funding source: DFG / Sonderforschungsbereich (SFB)
B01 zielt auf die kontinuumsbasierte Simulation der Regeneration von Rückenmarksgewebe nach Verletzungen oder Krankheiten ab. Die Modellierung und Simulation wird die zeitliche und räumliche Entwicklung von Wachstums-, Umbau- und Heilungsprozessen erfassen. Wir werden uns insbesondere auf mechanisch bedingte Prozesse konzentrieren, die an der Regeneration des Rückenmarks nach traumatischen Verletzungen und bei Multipler Sklerose beteiligt sind. Um die konstitutiven Modelle zu kalibrieren, werden wir mechanische Tests an menschlichem und tierischem Rückenmarksgewebe nutzen.
Modellierung und Simulation von Fehlbildungen des Gehirns (A01)
(Third Party Funds Group – Sub project)
Project leader: Silvia Budday
Term: 1. January 2023 - 31. December 2026
Acronym: SFB 1540 A01
Funding source: DFG / Sonderforschungsbereich (SFB)
A01 zielt darauf ab, ein Computermodell zu entwickeln, das die Mechanismen der abnormalen Gehirnentwicklung vorhersagt und die Diagnose und Behandlung von neurologischen Erkrankungen wie Epilepsie unterstützt. Basierend auf Erkenntnissen über das Zusammenspiel von Mechanik, Zellmigration, Zelldifferenzierung und Fehlbildungen des Gehirns aus den Projekten A02 bis A05 wird ein Mehrfeldmodell zur Vorhersage der physiologischen und pathologischen Gehirnentwicklung etabliert. Für die Modellkalibrierung und -validierung werden Datensätze aus dem Projekt A02 und mechanische Tests an bei chirurgischen Eingriffen entnommenen Hirngewebeproben verwendet.
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