MIT MechanoBiology Lab – Prof. Roger Kamm
(pioneering lab integrating microfluidics, tissue engineering, and computational modeling to study mechanobiology in neurodegenerative diseases)

MIT MechanoBiology Lab – Prof. Roger Kamm (pioneering lab integrating microfluidics, tissue engineering, and computational modeling to study mechanobiology in neurodegenerative diseases)
Challenge

Amyotrophic lateral sclerosis (ALS) progressively destroys motor neurons at the neuromuscular junction (NMJ). Disease mechanisms involve complex interactions between motor neurons, muscle cells, astrocytes, microglia, and the extracellular matrix—modulated by mechanical forces, fluid shear, and 3D microenvironmental cues. Traditional 2D cultures and animal models failed to recapitulate these multicellular, mechanobiological dynamics, leaving critical gaps in understanding NMJ degeneration and screening potential therapeutics.

How CytoSolve Helped

The Kamm Lab in collaboration with CytoSolve developed the world’s first full-scale computational systems architecture of the ALS neuromuscular junction microenvironment. CytoSolve’s platform:

  • Integrated molecular pathways governing neuronal excitability, synaptic transmission, glial activation, muscle contraction, and mechanotransduction from extensive peer-reviewed literature.
  • Incorporated multicellular crosstalk and biomechanical parameters (e.g., matrix stiffness, shear stress) into a dynamic, quantitative model.
  • Enabled in-silico simulation of ALS-relevant mutations and environmental perturbations within the 3D NMJ niche.

Key Benefits Realized

  • First Comprehensive NMJ Microenvironment Model
    Created an unprecedented systems-level architecture capturing the interplay of cellular, molecular, and mechanical factors driving NMJ degeneration in ALS.
  • Revealed Hidden Mechanobiological Mechanisms
    Uncovered non-obvious feedback loops and crosstalk—such as stiffness-dependent glial activation amplifying neuronal stress—previously inaccessible in reductionist models.
  • Novel Therapeutic Targets
    Identified high-leverage intervention nodes at the neuron–muscle–glia–matrix interface with predicted synergistic effects, guiding experimental validation in the lab’s microfluidic platforms.
  • Bridged Computation and Experiment
    Provided predictive mechanistic insights that directly informed design of advanced organ-on-chip models, accelerating hypothesis testing and therapeutic screening.

Outcome

The Kamm Lab in collaboration with CytoSolve achieved the first systems-level understanding of the ALS neuromuscular junction microenvironment, integrating mechanobiology with molecular pathology. This breakthrough has illuminated novel drivers of motor neuron degeneration, prioritized promising therapeutic strategies, and strengthened the lab’s leadership in neurodegenerative disease modeling—advancing the quest for effective ALS treatments. This collaboration highlights how CytoSolve’s infrastructure reveals the true multicellular, mechanobiological systems architecture of disease, empowering cutting-edge experimental labs to translate computation into transformative discoveries.