The Cellular Thermal Shift Assay (CETSA) is based on our discovery that the biophysical principle of ligand binding-induced thermal stabilization of proteins holds true for the proteins inside cells. CETSA coupled with mass spectrometry (MS-CETSA) has become a powerful discovery method for identifying drug targets and understanding drug actions on a proteome-wide scale. However, until recently, the use of CETSA for proteome-wide studies of cellular states with differential physiological interactions has not been fully explored. In a study of specific cell cycle phases in K562 cells, with a novel compact multidimensional MS-CETSA strategy, we uncovered modulations of interaction states for more than 750 proteins along the cell cycle, reflecting the biochemical processes such as protein phosphorylation, DNA binding and protein complex formation. Notably, many protein complexes are modulated in specific cell cycle phases, reflecting their roles in biological processes such as DNA replication, chromatin remodeling, transcription, translation, and nuclear membrane decomposition. Therefore, CETSA provides the first method for direct studies of the integrated modulation of protein interaction states (IMPRINTS) with physiological ligands in living cells. We believe this approach, which we refer to as IMPRINTS-CETSA, will open novel exciting opportunities to understand the operational aspects of cellular proteomes in intact cells and tissues.