Cell disruption is an inevitable step in many processes for the recovery of intracellular products. Currently, those processes are still energy-intensive and cost-ineffective, in particular with regard to low-cost bulk products such as biodiesel from microalgae. Characteristics of cell disruption were studied by compressive testing of single cells of Chlorella vulgaris with a nanoindenter. Results showed that bursting force as well as energy increased and the percentage of burst cells decreased with higher osmolality. The observations on microscopic level could also be transferred on macroscopic level using a stirred-media mill for cell disruption. The results of the cell disruption were compared to the findings of the compression tests and evaluated under energetic aspects.