The regulatory role of cell mechanics for migration of differentiating myeloid cells

Abstract

Migration of cells is important for tissue maintenance, immune response, and often altered in disease. While biochemical aspects, including cell adhesion, have been studied in detail, much less is known about the role of the mechanical properties of cells. Previous measurement methods rely on contact with artificial surfaces, which can convolute the results. Here, we used a non-contact, microfluidic optical stretcher to study cell mechanics, isolated from other parameters, in the context of tissue infiltration by acute promyelocytic leukemia (APL) cells, which occurs during differentiation therapy with retinoic acid. Compliance measurements of APL cells reveal a significant softening during differentiation, with the mechanical properties of differentiated cells resembling those of normal neutrophils. To interfere with the migratory ability acquired with the softening, differentiated APL cells were exposed to paclitaxel, which stabilizes microtubules. This treatment does not alter compliance but reduces cell relaxation after cessation of mechanical stress six-fold, congruent with a significant reduction of motility. Our observations imply that the dynamical remodeling of cell shape required for tissue infiltration can be frustrated by stiffening the microtubular system. This link between the cytokeleton, cell mechanics, and motility suggests treatment options for pathologies relying on migration of cells, notably cancer metastasis.acute promyelocytic leukemia ͉ cytoskeleton ͉ microtubules ͉ optical stretcher ͉ paclitaxel

Recent advances in microfluidic techniques for single-cell biophysical characterization

“…As a result, cell deformability can be used as an intrinsic marker for identifying pathological conditions. 8,19,20 For example, deformability is known to play a crucial role in the mobility of cancerous cells; 4,21 and a decrease in RBC deformability has been proven to be relevant in several human diseases (see Table 1). …”

“…1(b)), which combines a constriction channel and impedance measurements. 39 Detection involves only electrical signals; hence, it enables a throughput higher than 100 cells s 21 . The multiple parameters quantified as mechanical and electrical signatures include transit time, impedance amplitude ratio, and impedance phase increase.…”

“…The absolute mass and density were then determined and were used to distinguish malariainfected RBCs, RBCs from patients with sickle cell disease and thalassemia, and drug-treated leukemia cells. The microfluidic system has a testing speed of y500 cells h 21 .…”

“…For clinical applications, cell samples from pleural fluid, urine and blood are highly heterogeneous, and the number of cells of interest is usually low (e.g., CTC cells 21 . Although highspeed image recording and image analysis are a bottleneck, rapid advances in the imaging industry and hardware-based image processing could further enhance the clinical relevance of the microfluidic deformability cytometry technique.…”

Development of an advanced microfluidic micropipette aspiration device for single cell mechanics studies

“…[1][2][3] For example, cancer cells have been shown to be more deformable than their healthy counterparts in both patient clinical samples and different cancer (e.g., breast, bladder, cervix, pancreas, and ovarian) cell lines. [4][5][6] In addition, it is well recognized that cancer progression is accompanied by altered cytoskeletal architectures in cancer cells, causing them to be more deformable 2 and, in part, facilitate their metastatic journey out of a tumor into the blood stream.…”