The gastric digestion comprises three phases: physical disintegration, chemical breakdown and nutrient release. Controlling food proteins gelation conditions leads to the formation of particles with specific structural features that change protein digestibility. The development of foods with specific proteolysis rates allows their fit to different ‘nutritional vulnerable groups’ (newborn,elderly, obese, athletes) needs. The hypothesis is that the overall proteolysis reaction rate is limited by the pepsin diffusion rate within the protein structures generated in the stomach.Three milk gels with the same protein concentration but different microstructures were prepared either by rennet, acid coagulation of non-fat milk, or heat treatment of whey proteins. The disintegration of the different gel networks was investigated under digestion in simulated gastric conditions, and the effect of the acidic environment uncoupled from the enzyme effect. The first effect was monitored during 30 minutes before addition of pepsin for two hours of digestion.Kinetics of the process was surveilled by particle size measurements and matter loss.Proteolysis was characterized by SDS-PAGE, and diffusion of fluorescently labelled (FITC) pepsin within the gels was followed using fluorescent recovery after photobleaching with confocal microscopy. In contrast to acid and whey protein gels, rennet gels underwent large microstructural modifications under acidic conditions, forming extremely compact protein aggregates that significantly slowed down pepsin diffusion rates through the modified gel network. Microscopic observations showed slower morphological evolution during the enzymatic digestion, whose rates depended on the gel considered. Moreover, pepsin was able to diffuse within the aggregates.Recent microscopic observations obtained by tryptophan fluorescence imaging on the SOLEIL synchrotron DISCO beamline suggest that the particles were enzyme digested inside out. In this study, we succeeded in interpret the digestion phases as microstructural transformation,enzymatic reaction and diffusion phenomena in order to further dismantle the digestion process from a process engineering perspective.