Previous Image Next Image HA in layers When tissue overload occurs, there is an increase in the concentration of HA possibly due to a lack of the enzyme that metabolizes it (hyaluronidase). The HA molecules also cluster together (aggregate) which causes them to entangle. These events combined ultimately change the properties of HA from a space-creating lubricant in the extracellular matrix to a space occupying adherent. Courtesy of Antonio Stecco, MD, PhD. Tissue layers from skin to muscle showing areas where hyaluronic acid is more abundant and essential.