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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

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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.

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Long-term cell and nuclear trajectories and their correlations confirm the effectiveness of CN correlation approach in cell migration analysis.(a) A 500-minute cell trajectory (red dots) and its coupled nuclear trajectory (blue dots) are displayed at one-min time intervals. Dots are displayed with color gradients to indicate the instantaneous speeds. Trajectories from 100th to 200th, 200th to 300th, and 400th to 500th minutes are separately re-drawn with the corresponding barcodes. Black lines illustrate the temporal relationship between the two trajectories by connecting the cell and the corresponding nuclear positions in 50-minute time points. (b) Trajectories of cells are presented as a region-mixed barcode. Bars are aligned by their time sequences and each bar indicates a predominant subcellular migratory activity: detachment-dominant (red), mixed detachment and protrusion (yellow), protrusion-dominant (blue) and large-angle side protrusion (green). (c) Instant nucleus (blue) and cell (red) migratory speeds are shown, calculated by one-min time sequences. (d) Upper Row: CN correlations that occurred in Region I (red) or II (yellow) are depicted, where the value of NCD// is plotted against time sequences. Bottom Row: Moving averages of CMPI are plotted against the time at 10-min (blue) and one-hour (yellow) intervals.
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f3: Long-term cell and nuclear trajectories and their correlations confirm the effectiveness of CN correlation approach in cell migration analysis.(a) A 500-minute cell trajectory (red dots) and its coupled nuclear trajectory (blue dots) are displayed at one-min time intervals. Dots are displayed with color gradients to indicate the instantaneous speeds. Trajectories from 100th to 200th, 200th to 300th, and 400th to 500th minutes are separately re-drawn with the corresponding barcodes. Black lines illustrate the temporal relationship between the two trajectories by connecting the cell and the corresponding nuclear positions in 50-minute time points. (b) Trajectories of cells are presented as a region-mixed barcode. Bars are aligned by their time sequences and each bar indicates a predominant subcellular migratory activity: detachment-dominant (red), mixed detachment and protrusion (yellow), protrusion-dominant (blue) and large-angle side protrusion (green). (c) Instant nucleus (blue) and cell (red) migratory speeds are shown, calculated by one-min time sequences. (d) Upper Row: CN correlations that occurred in Region I (red) or II (yellow) are depicted, where the value of NCD// is plotted against time sequences. Bottom Row: Moving averages of CMPI are plotted against the time at 10-min (blue) and one-hour (yellow) intervals.

Mentions: To further evaluate the CN correlation approach, the cell and coupled nuclear trajectories from a single NIH 3T3 fibroblast were displayed and analyzed at one-minute intervals for a 500-minute duration (Fig. 3a; also see Supplementary Information 2: movie S5). Effective cell migration events exhibited by the trajectories were generally consistent with the barcode. Again, the active migratory cell with straight trajectory had 52% of the bars in the barcode located in Region I, significantly greater than the average rate, 24% (Fig. 3a, Box I and the corresponding barcode). When a large-angled turning event occurred (200th–300th min in the trajectories), the corresponding barcode contained 16% of bars in Region IV, relatively higher than the average rate, 11%. The presence of a higher frequency of negative NCD// supported our previous prediction that CN correlation data in the Region IV link to large-angle side protrusions (Fig. 3a, Box II and the corresponding barcode). In fact, this would be the signature in the barcode of the cell turning event and the major difference to separate the cell turning event from the evasive cell migration event (Fig. 3a, Box III and corresponding barcode).


Displacement correlations between a single mesenchymal-like cell and its nucleus effectively link subcellular activities and motility in cell migration analysis
Long-term cell and nuclear trajectories and their correlations confirm the effectiveness of CN correlation approach in cell migration analysis.(a) A 500-minute cell trajectory (red dots) and its coupled nuclear trajectory (blue dots) are displayed at one-min time intervals. Dots are displayed with color gradients to indicate the instantaneous speeds. Trajectories from 100th to 200th, 200th to 300th, and 400th to 500th minutes are separately re-drawn with the corresponding barcodes. Black lines illustrate the temporal relationship between the two trajectories by connecting the cell and the corresponding nuclear positions in 50-minute time points. (b) Trajectories of cells are presented as a region-mixed barcode. Bars are aligned by their time sequences and each bar indicates a predominant subcellular migratory activity: detachment-dominant (red), mixed detachment and protrusion (yellow), protrusion-dominant (blue) and large-angle side protrusion (green). (c) Instant nucleus (blue) and cell (red) migratory speeds are shown, calculated by one-min time sequences. (d) Upper Row: CN correlations that occurred in Region I (red) or II (yellow) are depicted, where the value of NCD// is plotted against time sequences. Bottom Row: Moving averages of CMPI are plotted against the time at 10-min (blue) and one-hour (yellow) intervals.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC5037420&req=5

f3: Long-term cell and nuclear trajectories and their correlations confirm the effectiveness of CN correlation approach in cell migration analysis.(a) A 500-minute cell trajectory (red dots) and its coupled nuclear trajectory (blue dots) are displayed at one-min time intervals. Dots are displayed with color gradients to indicate the instantaneous speeds. Trajectories from 100th to 200th, 200th to 300th, and 400th to 500th minutes are separately re-drawn with the corresponding barcodes. Black lines illustrate the temporal relationship between the two trajectories by connecting the cell and the corresponding nuclear positions in 50-minute time points. (b) Trajectories of cells are presented as a region-mixed barcode. Bars are aligned by their time sequences and each bar indicates a predominant subcellular migratory activity: detachment-dominant (red), mixed detachment and protrusion (yellow), protrusion-dominant (blue) and large-angle side protrusion (green). (c) Instant nucleus (blue) and cell (red) migratory speeds are shown, calculated by one-min time sequences. (d) Upper Row: CN correlations that occurred in Region I (red) or II (yellow) are depicted, where the value of NCD// is plotted against time sequences. Bottom Row: Moving averages of CMPI are plotted against the time at 10-min (blue) and one-hour (yellow) intervals.
Mentions: To further evaluate the CN correlation approach, the cell and coupled nuclear trajectories from a single NIH 3T3 fibroblast were displayed and analyzed at one-minute intervals for a 500-minute duration (Fig. 3a; also see Supplementary Information 2: movie S5). Effective cell migration events exhibited by the trajectories were generally consistent with the barcode. Again, the active migratory cell with straight trajectory had 52% of the bars in the barcode located in Region I, significantly greater than the average rate, 24% (Fig. 3a, Box I and the corresponding barcode). When a large-angled turning event occurred (200th–300th min in the trajectories), the corresponding barcode contained 16% of bars in Region IV, relatively higher than the average rate, 11%. The presence of a higher frequency of negative NCD// supported our previous prediction that CN correlation data in the Region IV link to large-angle side protrusions (Fig. 3a, Box II and the corresponding barcode). In fact, this would be the signature in the barcode of the cell turning event and the major difference to separate the cell turning event from the evasive cell migration event (Fig. 3a, Box III and corresponding barcode).

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.


Related in: MedlinePlus