Neural signaling of skin sensory perception from topical treatments is often reported in subjective terms such as a sensation of skin “tightness” after using a cleanser or “softness” after applying a moisturizer. However, the mechanism whereby cutaneous mechanoreceptors and corresponding sensory neurons are activated giving rise to these perceptions has not been established. Here, we provide a quantitative approach that couples in vitro biomechanical testing and detailed computational neural stimulation modeling along with a comprehensive in vivo self-assessment survey to demonstrate how cutaneous biomechanical changes in response to treatments are involved in the sensorial perception of the human skin.