This is the final version of the article. Available from the publisher via the DOI in this record.Although cellular mechanical properties are known to alter during stem cell differentiation, understanding of the functional relevance of such alterations is incomplete. Here, we show that during the course of differentiation of human myeloid precursor cells into three different lineages, the cells alter their viscoelastic properties, measured using an optical stretcher, to suit their ultimate fate and function. Myeloid cells circulating in blood have to be advected through constrictions in blood vessels, engendering the need for compliance at short time-scales (minutes), compared to undifferentiated cells. These findings suggest that reduction in steady-state viscosity is a physiological adaptation for enhanced migration through tissues. Our results indicate that the material properties of cells define their function, can be used as a cell differentiation marker and could serve as target for novel therapies.Funding: The authors acknowledge financial support by the Cambridge Commonwealth Trust (to AEE; http://www.cambridgetrusts.org), the Medical Research
Council (to KC and JG; grant number: 94185; http://www.mrc.ac.uk), the Human Frontier Science Program (to GW and JG; grant number: RGP0015/2009-C; http://
www.hfsp.org) and the European Research Council (to JG; grant number: 282060; http://erc.europa.eu)
