1. Electromechanics and Volume Dynamics in Nonexcitable Tissue Cells
Florence Yellin, Yizeng Li, Varun K.A. Sreenivasan, Brenda Farrell, Manu B. Johny, David Yue, Sean X. Sun 
Biophysical Journal 
Volume 114, Issue 9, Pages (May 2018)
DOI: /j.bpj
Copyright © 2018 Biophysical Society Terms and Conditions

2. Figure 1
Cell volume regulation on short timescales is closely related to ionic regulation. Major ion species in the cell are Na+, K+, and Cl−, which are all present in millimolar concentrations. These ion concentrations are controlled by passive ion channels and active ion pumps. Changes in ionic content also influence the transmembrane potential. In experiments, the membrane potential can be controlled by introducing external currents using a voltage clamp. The cell volume, which is determined by the overall water and protein content, can be modulated by changes in the transmembrane potential, external ionic content, or cortical tension. To see this figure in color, go online.
Biophysical Journal  , DOI: ( /j.bpj )
Copyright © 2018 Biophysical Society Terms and Conditions

3. Figure 2
Cell volume correlates with the transmembrane potential. (A) As the membrane holding potential is changed (upper panel), the cell radius and volume change with time (lower panel). The data is shown for one cell for illustration. (B) Shown here is the measured steady-state cell volume-versus-transmembrane potential after the cell has completed its response. Cell volume is normalized with respect to the volume at −60 mV. The volume increases with depolarization. (Star) Shown here is the experimental data. Different colors represent different cells (N = 10). The following are the significance of cell volume change for each voltage condition when compared to Vm = −60 mV according to the Student t-test. 0 mV: p = , n = 7; −90 mV: p = , n = 5; −110 mV: p = 0, n = 2; −120 mV: p = , n = 6. (Solid line) Given here is the model prediction. (C) Model prediction is shown on the intracellular concentrations of the four species as functions of the membrane potential. To see this figure in color, go online.
Biophysical Journal  , DOI: ( /j.bpj )
Copyright © 2018 Biophysical Society Terms and Conditions

4. Figure 3
Cell volume correlates with the extracellular chloride concentration. (A) Cells were suspended using a micropipette, the extracellular medium was changed to low-chloride solution, and the cell volume was simultaneously monitored. The pipette was simply to hold the cell in suspension while measuring its size. (B) The measured cell volume is shown for a single HN31 cell as a function of time during chloride solution switch. The upper panel indicates the time of medium switch; because the low-chloride medium gradually flows into the solution, the exact profile of the chloride concentration is not a perfect step function. In the upper panel we use a step function only to indicate the time of medium switch. (C) Cell volume shows an ∼10% decrease as chloride decreases in the extracellular medium. (Star) Shown here is experimental data, n = 6, mean ± SD = 0.81 ± 0.09, p = according to the Student t-test. (Solid line) Given here is the model prediction. (D) Model prediction of the membrane potential is shown as a function of the extracellular chloride concentration. (E) Model prediction is given on the intracellular ionic contents of the four species as functions of the extracellular chloride concentration. In this model, we let αNKCC = 1.5 × 10−10 mol/m2/s to account for the cellular response to the medium shock with low chloride. To see this figure in color, go online.
Biophysical Journal  , DOI: ( /j.bpj )
Copyright © 2018 Biophysical Society Terms and Conditions

5. Figure 4
(A) Cells were slightly compressed in the compression microfluidic device and were held in place to avoid being washed away by the medium. The supporting pillars were used to support the compression chamber and to avoid cells being overcompressed. A confocal Z-stack reconstruction of the cell demonstrated that the cells were still close to spheres. We also performed control experiments to measure cell volume fluctuation without environmental perturbation. Volumes of each cell were measured ∼1 h apart. The histogram is shown for n = 31 cells with mean ± SD = ± (B) Experimental data shows that the cell volume increases in the low-sodium/high-potassium medium; n = 19, mean ± SD = 1.58 ± 0.33, p = 4.186 × 10−7 according to the Student t-test. (C) New medium with dye was flowed into the device, and different regions of the device were imaged. The dye time-series data for different regions of the device shows that the medium mixing is not uniform. Here we show the dye intensity at three sample nearby locations in the channel. (D) Model prediction of the cell volume and the membrane potential are given as the external sodium is gradually replaced by potassium. (E) Model prediction of the intracellular ionic contents is given as the external sodium is gradually replaced by potassium. In this model, the following parameters are adjusted to account for the cellular response to the medium shock: αATP = 1 m/s, αNa/K,Na = 5, αNa/K,K = 0.01, αNKCC = 1 × 10−13 mol/m2/s. These parameters are mostly involved in the Na/K pump. To see this figure in color, go online.
Biophysical Journal  , DOI: ( /j.bpj )
Copyright © 2018 Biophysical Society Terms and Conditions

6. Figure 5
The role of the actin cortex in maintaining cell volume. (A) Schematics show that depolymerizing actin disrupts the cortex and reduces active contractile stress in the cortex, leading to a cell volume increase (not to scale). (B) Experimental data show that cell volume increases upon actin depolymerization; n = 38, mean ± SD = 1.06 ± 0.087, p = according to the Student t-test. The control data is shown in Fig. 4 A. (C) Model prediction is given on the cell volume and the membrane potential when Lat. A is added to the cell. (D) Model prediction is given of the concentrations of the intracellular species. In this model we let αATP = 0.25 and let the effective membrane thickness vary linearly from 500 to 10 nm as the contractile stress decreases. To see this figure in color, go online.
Biophysical Journal  , DOI: ( /j.bpj )
Copyright © 2018 Biophysical Society Terms and Conditions

7. Figure 6
(A) Model prediction of the cell volume (left axis) and the membrane potential (right axis) are shown as functions of the intracellular protein content. (B) Model prediction is given of the intracellular ion and protein concentrations with the intracellular protein content. (C) Model prediction is shown of the cell volume with the combined total intracellular ion and protein contents from the four experiments: voltage clamp, low-chloride medium, low-sodium/high-potassium medium, and actin depolymerization. (Inset) Given here is a zoom-in for better visualization of the curve for actin depolymerization. (D) Schematic explains the volume-content relation during actin depolymerization (not to scale). Each solid curve represents a generic volume-content relation for a fixed cortical tension, similar to the chloride depletion curve, for example, in (C). A trajectory connecting different points on different solid lines gives the actin depolymerization curve in (C). (E) Model predictions are given of the equilibrium ion concentrations when the flux of Na+/K+ pump is reduced. This panel is a counterpart of (B). Here αATP is 10% of the original value. The model predicts that in this case the cell is unable to maintain a low intracellular sodium concentration and a high intracellular potassium concentration. To see this figure in color, go online.
Biophysical Journal  , DOI: ( /j.bpj )
Copyright © 2018 Biophysical Society Terms and Conditions