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Updated: May 24, 2026
07:39
Induction of Acute Skeletal Muscle Regeneration by Cardiotoxin Injection
Published on: January 1, 2017
Biochemical and mechanical environment cooperatively regulate skeletal muscle regeneration
Sarah Calve1, Hans-Georg Simon
1Department of Pediatrics, Northwestern University, Feinberg School of Medicine, Children's Memorial Research Center, Chicago, Illinois 60614, USA.
Summary
Newt muscle regeneration relies on a softer extracellular matrix (ECM) that promotes cell migration. This study reveals how ECM stiffness and composition influence cell behavior during limb regrowth.
Area of Science:
- Regenerative Biology
- Extracellular Matrix Biology
- Muscle Cell Biology
Background:
- Forelimb regeneration in newts involves dynamic extracellular matrix (ECM) expression.
- The role of ECM remodeling, tissue stiffness, and mechanical variations in newt muscle regeneration was previously unknown.
Purpose of the Study:
- To investigate the influence of ECM composition and stiffness on skeletal muscle cell behavior during regeneration.
- To correlate in vitro findings with in vivo observations of newt limb regeneration.
Main Methods:
- Measured transverse stiffness of newt tissues in situ.
- Coated silicone substrates with varying stiffness (2-100 kPa) and ECM components (tenascin-C, fibronectin, laminin, Matrigel).
- Utilized live-cell imaging to observe muscle cell fragmentation, migration, and fusion.
Main Results:
- Undifferentiated blastemas were less stiff than differentiated muscle (13.3±1.6 vs. 16.6±1.2 kPa).
- Softer substrates with tenascin-C enhanced muscle cell migration and fragmentation.
- Stiffer substrates promoted differentiation while inhibiting migration and fragmentation.
Conclusions:
- A transitional ECM with reduced stiffness regulates muscle plasticity and progenitor cell recruitment during newt regeneration.
- Biochemical and mechanical cues from the ECM control genetic pathways driving regeneration.
- Findings provide insights into optimizing regenerative strategies by manipulating ECM properties.
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