Viscoelastic Properties of Differentiating Blood Cells Are Fate- and Function-Dependent

Abstract

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 (<seconds). Intriguingly, only the two circulating myeloid cell types have increased short time scale compliance and flow better through microfluidic constrictions. Moreover, all three differentiated cell types reduce their steady-state viscosity by more than 50% and show over 140% relative increase in their ability to migrate through tissue-like pores at long 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.

Nuclear Envelope Composition Determines the Ability of Neutrophil-type Cells to Passage through Micron-scale Constrictions

“…HL-60 cells also exhibit similar mechanical properties; recent measurements of cell compliance using an optical stretcher confirmed that in vitro differentiation of HL-60 cells into neutrophil-type cells recapitulates the 3-6-fold increase in cell deformability observed in primary neutrophils and their CD34ϩ precursor cells (31). A direct comparison of the absolute passage times through micron-sized constriction between primary neutrophils and HL-60-derived neutrophil-type cells is complicated by the fact that HL-60 cells are typically larger than primary neutrophils (ϳ12-m versus 7-8-m median diameter, respectively) and exhibit substantially larger transit times through microfluidic constriction channels (29).…”

Nanobiomechanics of living cells: a review

“…Alterations in cell properties are of fundamental importance for a wide range of processes, and changes in cell mechanics are associated with conditions such as osteoarthritis [8], asthma [9], cancer [10], inflammation [11] and malaria [12]. The mechanical properties of living cells have been quantified using various testing methods, such as micropipette aspiration [8,13], magnetic twisting cytometry [14], optical tweezers [15][16][17] and nanoindentation [18][19][20].…”

Blood viscoelasticity measurement using steady and transient flow controls of blood in a microfluidic analogue of Wheastone-bridge channel

“…17 Most of these methods require fully integrated sensors or additional tedious calibration procedure using a standard reference. On the other hand, viscoelasticity measurement of fluids has been conducted using ferromagnetic micro-beads, 18 optically-induced force, 19 squeeze flows, 20,21 flexible polymer-based deflection, 22,23 micro-PIV, 24 and extensional flow. 25,26 However, most of these previous studies focused on measuring the relaxation time rather than elasticity itself because these methods may not have the ability to concurrently measure fluid viscosity.…”