The mechanical properties of cells change with their differentiation,chronological age,and malignant progression.Consequently,these properties may be useful label-free biomarkers of various functional or clinically re...The mechanical properties of cells change with their differentiation,chronological age,and malignant progression.Consequently,these properties may be useful label-free biomarkers of various functional or clinically relevant cell states.Here,we demonstrate mechano-node-pore sensing(mechano-NPS),a multi-parametric single-cell-analysis method that utilizes a four-terminal measurement of the current across a microfluidic channel to quantify simultaneously cell diameter,resistance to compressive deformation,transverse deformation under constant strain,and recovery time after deformation.We define a new parameter,the whole-cell deformability index(wCDI),which provides a quantitative mechanical metric of the resistance to compressive deformation that can be used to discriminate among different cell types.The wCDI and the transverse deformation under constant strain show malignant MCF-7 and A549 cell lines are mechanically distinct from non-malignant,MCF-10A and BEAS-2B cell lines,and distinguishes between cells treated or untreated with cytoskeleton-perturbing small molecules.We categorize cell recovery time,ΔT_(r),as instantaneous(ΔTr~0 ms),transient(ΔT_(r)≤40 ms),or prolonged(ΔT_(r)>40 ms),and show that the composition of recovery types,which is a consequence of changes in cytoskeletal organization,correlates with cellular transformation.Through the wCDI and cell-recovery time,mechano-NPS discriminates between sub-lineages of normal primary human mammary epithelial cells with accuracy comparable to flow cytometry,but without antibody labeling.Mechano-NPS identifies mechanical phenotypes that distinguishes lineage,chronological age,and stage of malignant progression in human epithelial cells.展开更多
基金This research was partially funded by National Institutes of Health 1R01CA190843-01(LLS),1R21CA182375-01A1(LLS),1R21EB019181-01A1(LLS),R01AG040081(MAL),and DP2 HD080351-01(ZJG)the Department of Defense Breast Cancer Research Program Era of Hope Scholar Award BC141351(MAL)the Department of Defense Breast Cancer Research Program grants W81XWH-10-1-1023(ZJG)and W81XWH-13-1-0221(ZJG).
文摘The mechanical properties of cells change with their differentiation,chronological age,and malignant progression.Consequently,these properties may be useful label-free biomarkers of various functional or clinically relevant cell states.Here,we demonstrate mechano-node-pore sensing(mechano-NPS),a multi-parametric single-cell-analysis method that utilizes a four-terminal measurement of the current across a microfluidic channel to quantify simultaneously cell diameter,resistance to compressive deformation,transverse deformation under constant strain,and recovery time after deformation.We define a new parameter,the whole-cell deformability index(wCDI),which provides a quantitative mechanical metric of the resistance to compressive deformation that can be used to discriminate among different cell types.The wCDI and the transverse deformation under constant strain show malignant MCF-7 and A549 cell lines are mechanically distinct from non-malignant,MCF-10A and BEAS-2B cell lines,and distinguishes between cells treated or untreated with cytoskeleton-perturbing small molecules.We categorize cell recovery time,ΔT_(r),as instantaneous(ΔTr~0 ms),transient(ΔT_(r)≤40 ms),or prolonged(ΔT_(r)>40 ms),and show that the composition of recovery types,which is a consequence of changes in cytoskeletal organization,correlates with cellular transformation.Through the wCDI and cell-recovery time,mechano-NPS discriminates between sub-lineages of normal primary human mammary epithelial cells with accuracy comparable to flow cytometry,but without antibody labeling.Mechano-NPS identifies mechanical phenotypes that distinguishes lineage,chronological age,and stage of malignant progression in human epithelial cells.
