Cell deformability heterogeneity recognition by unsupervised machine learning from in-flow motion parameters

Abstract

Cell deformability is a well-established marker of cell states for diagnostic purposes. However, the measurement of a wide range of different deformability levels is still challenging, especially in cancer, where a large heterogeneity of rheological/mechanical properties is present. Therefore, a simple, versatile and cost-effective recognition method for variable rheological/mechanical properties of cells is needed. Here, we introduce a new set of in-flow motion parameters capable of identifying heterogeneity among cell deformability, properly modified by the administration of drugs for cytoskeleton destabilization. Firstly, we measured cell deformability by identification of in-flow motions, rolling (R), tumbling (T), swinging (S) and tank-treading (TT), distinctively associated with cell rheological/mechanical properties. Secondly, from a pool of motion and structural cell parameters, an unsupervised machine learning approach based on principal component analysis (PCA) revealed dominant features: the local cell velocity (VCell/VAvg), the equilibrium position (YEq) and the orientation angle variation (Δφ). These motion parameters clearly defined cell clusters in terms of motion regimes corresponding to specific deformability. Such correlation is verified in a wide range of rheological/mechanical properties from the elastic cells moving like R until the almost viscous cells moving as TT. Thus, our approach shows how simple motion parameters allow cell deformability heterogeneity recognition, directly measuring rheological/mechanical properties.