Mechanical strain and BMP-stimulation instruct the extracellular matrix to control stem cell fate decisions: an age-dependent matrix code?

• Applicants: Professorin Dr. Petra Knaus; Professor Dr. Ansgar Petersen
• Subject Area: Orthopaedics, Traumatology, Reconstructive Surgery
• Term: from 2014 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 249509554

Already in the very early phase of bone fracture healing, a complex extracellular matrix (ECM) network is assembled. The biochemical and mechanical signals provided by the ECM are believed to instruct cell fate and function. We hypothesize that the information encoded in the ECM is modulated by the physico-chemical stimuli present during its formation and that the stored information will be sensed by cells much longer than the stimuli were present. We will build ECM in 3D microtissue culture under control of mechanical straining and bone morphogenetic proteins (BMPs) and perform careful mechanical and biochemical characterization. We will furthermore study the instructiveness of decellularized matrices on bone progenitor cells and investigate the influence of ageing on the encoding and reading process. We propose that the ECM plays a relevant role as an age-dependent memory for mechanical and biochemical signals during bone regeneration.

• DFG Programme: Research Units
• Subproject of: FOR 2165: Regeneration in Aged Individuals: Using Bone Healing as a Model System to Characterise Regeneration under Compromised Conditions