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Displacement correlations between a single mesenchymal-like cell and its nucleus effectively link subcellular activities and motility in cell migration analysis

View Article: PubMed Central - PubMed

ABSTRACT

Cell migration is an essential process in organism development and physiological maintenance. Although current methods permit accurate comparisons of the effects of molecular manipulations and drug applications on cell motility, effects of alterations in subcellular activities on motility cannot be fully elucidated from those methods. Here, we develop a strategy termed cell-nuclear (CN) correlation to parameterize represented dynamic subcellular activities and to quantify their contributions in mesenchymal-like migration. Based on the biophysical meaning of the CN correlation, we propose a cell migration potential index (CMPI) to measure cell motility. When the effectiveness of CMPI was evaluated with respect to one of the most popular cell migration analysis methods, Persistent Random Walk, we found that the cell motility estimates among six cell lines used in this study were highly consistent between these two approaches. Further evaluations indicated that CMPI can be determined using a shorter time period and smaller cell sample size, and it possesses excellent reliability and applicability, even in the presence of a wide range of noise, as might be generated from individual imaging acquisition systems. The novel approach outlined here introduces a robust strategy through an analysis of subcellular locomotion activities for single cell migration assessment.

No MeSH data available.


A sample size of 20 one-hour cell migration movies is sufficient to derive precise and accurate CMPI for cell motility description.(a) Means and variances of CMPI are plotted against sample size for 6 different types of cells. Error bars represent standard error of the mean. (b) Correlation between CMPIs and diffusion coefficients for 6 different cell types. A blue dot represents a cell type, and the dashed line is the fitting curve. Abbreviations for cell types: MDA-MB-231 (MDA), NIH 3T3 (NIH), SKOV-3 (SKOV), OVCAR-3 (OVCAR), U-2 OS (U2OS), SWISS 3T3 (SWISS) and Human Foreskin Fibroblasts (HFF).
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f4: A sample size of 20 one-hour cell migration movies is sufficient to derive precise and accurate CMPI for cell motility description.(a) Means and variances of CMPI are plotted against sample size for 6 different types of cells. Error bars represent standard error of the mean. (b) Correlation between CMPIs and diffusion coefficients for 6 different cell types. A blue dot represents a cell type, and the dashed line is the fitting curve. Abbreviations for cell types: MDA-MB-231 (MDA), NIH 3T3 (NIH), SKOV-3 (SKOV), OVCAR-3 (OVCAR), U-2 OS (U2OS), SWISS 3T3 (SWISS) and Human Foreskin Fibroblasts (HFF).

Mentions: We hypothesized that the averaged CMPI value (expressed as <CMPI>) from multiple cells of a cell type might be used to represent the motility of the cell type. To test this hypothesis, we first evaluated the precision of <CMPI> against the cell sample size. The cell types studied included 3 cancer cell lines: MDA-MB-231, SKOV-3, and U-2 OS cells, and 3 fibroblast lines: NIH 3T3, Swiss 3T3, and human foreskin fibroblasts. <CMPI> of each cell type was calculated from different cell sample sizes. At each iteration, samples of each cell type were independently and randomly chosen from a pool of 50 samples and cell sample size was increased by a step of 5. At small sample sizes (1-min time intervals and one-hour monitoring time), the <CMPI> of all six cell types fluctuated. However, when the sample size exceeded 20, the <CMPI> approached a steady state, in which the standard error of the mean diminished to the confidence limit (less than 10% of the mean value) (Fig. 4a). These results indicate that a stable <CMPI>, i.e., exhibiting a good convergent tendency, can be obtained from a relatively small cell sample size (~20).


Displacement correlations between a single mesenchymal-like cell and its nucleus effectively link subcellular activities and motility in cell migration analysis
A sample size of 20 one-hour cell migration movies is sufficient to derive precise and accurate CMPI for cell motility description.(a) Means and variances of CMPI are plotted against sample size for 6 different types of cells. Error bars represent standard error of the mean. (b) Correlation between CMPIs and diffusion coefficients for 6 different cell types. A blue dot represents a cell type, and the dashed line is the fitting curve. Abbreviations for cell types: MDA-MB-231 (MDA), NIH 3T3 (NIH), SKOV-3 (SKOV), OVCAR-3 (OVCAR), U-2 OS (U2OS), SWISS 3T3 (SWISS) and Human Foreskin Fibroblasts (HFF).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5037420&req=5

f4: A sample size of 20 one-hour cell migration movies is sufficient to derive precise and accurate CMPI for cell motility description.(a) Means and variances of CMPI are plotted against sample size for 6 different types of cells. Error bars represent standard error of the mean. (b) Correlation between CMPIs and diffusion coefficients for 6 different cell types. A blue dot represents a cell type, and the dashed line is the fitting curve. Abbreviations for cell types: MDA-MB-231 (MDA), NIH 3T3 (NIH), SKOV-3 (SKOV), OVCAR-3 (OVCAR), U-2 OS (U2OS), SWISS 3T3 (SWISS) and Human Foreskin Fibroblasts (HFF).
Mentions: We hypothesized that the averaged CMPI value (expressed as <CMPI>) from multiple cells of a cell type might be used to represent the motility of the cell type. To test this hypothesis, we first evaluated the precision of <CMPI> against the cell sample size. The cell types studied included 3 cancer cell lines: MDA-MB-231, SKOV-3, and U-2 OS cells, and 3 fibroblast lines: NIH 3T3, Swiss 3T3, and human foreskin fibroblasts. <CMPI> of each cell type was calculated from different cell sample sizes. At each iteration, samples of each cell type were independently and randomly chosen from a pool of 50 samples and cell sample size was increased by a step of 5. At small sample sizes (1-min time intervals and one-hour monitoring time), the <CMPI> of all six cell types fluctuated. However, when the sample size exceeded 20, the <CMPI> approached a steady state, in which the standard error of the mean diminished to the confidence limit (less than 10% of the mean value) (Fig. 4a). These results indicate that a stable <CMPI>, i.e., exhibiting a good convergent tendency, can be obtained from a relatively small cell sample size (~20).

View Article: PubMed Central - PubMed

ABSTRACT

Cell migration is an essential process in organism development and physiological maintenance. Although current methods permit accurate comparisons of the effects of molecular manipulations and drug applications on cell motility, effects of alterations in subcellular activities on motility cannot be fully elucidated from those methods. Here, we develop a strategy termed cell-nuclear (CN) correlation to parameterize represented dynamic subcellular activities and to quantify their contributions in mesenchymal-like migration. Based on the biophysical meaning of the CN correlation, we propose a cell migration potential index (CMPI) to measure cell motility. When the effectiveness of CMPI was evaluated with respect to one of the most popular cell migration analysis methods, Persistent Random Walk, we found that the cell motility estimates among six cell lines used in this study were highly consistent between these two approaches. Further evaluations indicated that CMPI can be determined using a shorter time period and smaller cell sample size, and it possesses excellent reliability and applicability, even in the presence of a wide range of noise, as might be generated from individual imaging acquisition systems. The novel approach outlined here introduces a robust strategy through an analysis of subcellular locomotion activities for single cell migration assessment.

No MeSH data available.