Mechanobiology in the Brain: Sensing Your Heartbeats via Mechanosensitive Channels

The brain-heart axis mediates bidirectional communication via neural and humoral pathways and plays a pivotal role in physiological regulation and the pathogenesis of cardiocerebral comorbidities. Mechanobiological studies further suggest that mechanical signaling pathways may serve as the third modality for brain-heart crosstalk. This commentary reviews two distinct mechanical regulatory modalities within the brain-heart axis: periphery-dependent mechanosensation, which acts as an upstream sensory module of classical neural pathways, and central in-situ mechanotransduction, which directly senses mechanical stimuli originating from cardiovascular pulsations in the central nervous system. Cumulative molecular, ex vivo, and in vivo experimental evidence demonstrates that subsets of central neurons can directly respond to arterial pressure pulsations via mechanosensitive ion channels and achieve functional coupling with heartbeat rhythms. Nevertheless, this field faces further evidentiary limitations. This commentary synthesizes current evidence and puts forward a scientific hypothesis that the mechanical microenvironment of brain tissue may modulate central mechanosensation. It also highlights future priorities including verification across broader neuronal cell types and in vivo functional interventions, to further refine the theoretical framework of the brain-heart axis.