Project Details
Projekt
Skeletal Muscle Adaptation: the cornerstone for modelling neuromuscular diseases and predicting muscular deficiencies (Identification, Homogenisation, Verification, and Integration)
Applicants
Dr. Filiz Ates; Professor Oliver Röhrle, Ph.D.
Subject Area
Applied Mechanics, Statics and Dynamics
Term
since 2021
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 465195108
The importance of the extracellular matrix (ECM) has been highlighted in many applications. It determines the nature of some genetic and acquired diseases. Understanding structure and function of the ECM would help to clarify mechanisms of aging, training, and muscle injury. Only a very limited number of studies focused on structural changes of the ECM and even a fewer investigated its impact to the organ. One of the key missing parts hereby is the lack of understanding how the ECM mechanically acts within activatable tissues. To close some aspects of this gap, we choose to investigate a clinical case: intramuscular connective tissue and its adaptive response to botulinum toxin administration. It is a standard clinical practice to diminish spasticity. However, muscles exposed to toxin show fibrosis-like alterations. We aim to investigate skeletal muscle fiber adaptation by (i) designing new experimental setups, (ii) using experimental insights to postulate novel microstructural models of ECM adaptation that integrate measurable data on the microstructure as well as (iii) validating the model against available data and existing hypothesis. Further, we develop homogenisation methods to integrate the microstructurally-based fiber-ECM adaptation model on the skeletal muscle scale. By doing so, we find new ways to investigate the impact of ECM adaptation to larger scales. In addition, the combination of experimental and computational research empowers us to provide additional information that is hardly measurable, in particular not with the desired resolution, e.g. the material composition at ``infinite'' time points that support clinician in the decision-making process in terms of treatment. We follow hereby the keywords: Identification; identifying the underlying base processes leading to adaptation collecting experimental data and computational approaches, Homogenisation; formulating a bottom-up microstructural approach rather than a phenomenological model, Validation; examining existing hypotheses, and Integration; integrating the model to larger scales, such as entire muscle or whole musculoskeletal system.
DFG Programme
Priority Programmes
