Substrate stiffness affects neural network activity in an extracellular matrix proteins dependent manner

Area of Science:

• Neuroscience
• Biomaterials Science
• Cellular Mechanics

Background:

• Neuronal functions like growth, differentiation, and network activity are influenced by the mechanical properties of the extracellular matrix (ECM).
• The precise mechanisms by which substrate stiffness regulates neural network activity and the role of ECM composition in sensing stiffness remain underexplored.

Purpose of the Study:

• To investigate how substrate stiffness affects neural network activity in hippocampal neurons.
• To determine the influence of extracellular matrix composition (fibronectin vs. laminin) on neuronal responses to substrate stiffness.

Main Methods:

• Hippocampal neurons were cultured on polydimethylsiloxane (PDMS) substrates with varying stiffness.
• Substrates were coated with either fibronectin or laminin.
• Voltage-gated calcium channel currents and paired patch-clamp recordings were used to assess neural activity and synaptic connectivity.

Main Results:

• Neurons on stiffer substrates exhibited greater voltage-gated calcium channel currents compared to those on softer substrates.
• Laminin-coated stiff substrates resulted in a more significant increase in calcium currents and synaptic connectivity compared to fibronectin-coated substrates.
• Laminin-coated stiff substrates enhanced neuronal calcium oscillations more than fibronectin-coated substrates.

Conclusions:

• Substrate stiffness directly regulates neuronal network activity.
• The specific composition of the extracellular matrix protein modulates neuronal responses to substrate stiffness.
• These findings are crucial for designing biomaterials for neuronal tissue engineering, emphasizing the need to consider ECM protein type.