SUMMARY
In an otherwise healthy individual, the feeling of urinary bladder fullness integrates two important pieces of
information: (1) urine is collecting and can be stored; and (2) the amount of urine collected has reached a point
that voiding is a necessity. While countless papers claim to identify the source(s) of bladder dysfunction, they do
so without the most basic understanding of why we feel the need to void. Interestingly, many bladder pathologies
(whether overactivity or underactivity) both present with dramatic changes in the structure and mechanical
properties of the urinary bladder wall. Changes to these properties are often assumed to be the effect, not the
cause, of bladder dysfunction. We discovered that bladder wall biomechanics inexorably connect to the
perception of bladder fullness even in healthy individuals. This proposal seeks to understand and define how the
microstructure of the bladder wall transduces changes in bladder volume to the CNS, in the absence of any
confounding pathology, and finally determine what causes the sensation of bladder fullness. Drawing on our
interdisciplinary expertise in engineering and physiology, we will use innovative tools, genetic mouse models,
and biomechanical modeling to elucidate the relationship between elasticity, viscosity, and sensory outflow.
Through these experiments, we will not only learn the relationship between bladder wall mechanics,
microstructural organization, and afferent outflow, but we will also determine how the spatial arrangement of
transient UBSM contractions influences the sensation of fullness. This represents a paradigm shift in our
understanding of how biomechanics and physiology intersect to drive mechanosensation.