Changes In Cell Mass Research Articles

Should I shrink or should I grow: cell size changes in tissue morphogenesis.

Cells change shape, move, divide, and die to sculpt tissues. Common to all these cell behaviours are cell size changes, which have recently emerged as key contributors to tissue morphogenesis. Cells can change their mass-the number of macromolecules they contain-or their volume-the space they encompass. Changes in cell mass and volume occur through different molecular mechanisms and at different timescales, slow for changes in mass and rapid for changes in volume. Therefore, changes in cell mass and cell volume, which are often linked, contribute to the development and shaping of tissues in different ways. Here, we review the molecular mechanisms by which cells can control and alter their size, and we discuss how changes in cell mass and volume contribute to tissue morphogenesis. The role that cell size control plays in developing embryos is only starting to be elucidated. Research on the signals that control cell size will illuminate our understanding of the cellular and molecular mechanisms that drive tissue morphogenesis.

Evolution of body composition following successful kidney transplantation is strongly influenced by physical activity: results of the CORPOS study

BackgroundWeight gain (mainly gain of fat mass) occurs quickly after successful kidney transplantation and is associated with metabolic complications (alterations of glycaemic control, hyperlipidaemia). Determinants of weight gain are multifactorial and are mainly related to the transplant procedure itself (glucocorticoid use, increased appetite). In the modern era of transplantation, one challenge is to limit these metabolic alterations by promoting gain of muscle mass rather than fat mass. This prospective study was performed to assess determinants of fat mass, fat-free mass and body cell mass changes after kidney transplantation with a focus on physical activity and nutritional behaviour before and after transplantation.MethodsPatients were included at the time of listing for deceased donor kidney transplantation. Body composition was determined using dual X-ray absorptiometry and bioimpedance spectroscopy to assess fat mass, fat-free mass and body cell mass (= fat-free mass − extracellular water) at the time of inclusion, 12 months later, and 1, 6, 12 and 24 months after transplantation. Recall dietary data and physical activity level were also collected.ResultsEighty patients were included between 2007 and 2010. Sixty-five had a complete 24-month follow-up after kidney transplantation. Fat mass, fat-free mass and body cell mass decreased during the waiting period and early after kidney transplantation. The nadirs of body cell mass and fat-free mass occurred at 1 month and the nadir for fat mass occurred at 6 months. Maximum levels of all parameters of body composition were seen at 12 months, after which body cell mass and fat-free mass decreased, while fat mass remained stable. In multivariate analysis, male recipients, higher physical activity level and lower corticosteroid dose were significantly associated with better body cell mass recovery after kidney transplantation.ConclusionsLifestyle factors, such as physical activity level, together with low dose of corticosteroids seem to influence body composition evolution following kidney transplantation with recovery of body cell mass. Specific strategies to promote physical activity in kidney transplant recipients should be provided before and after kidney transplantation.

Regulatory effect of apoptosis on morphological changes in cell mass of porcine blastocyst through supplementation of rapamycin during in vitro culture

Objective:The study of an in vitro embryosis is crucial in genetics for breed improvement and reproduction in livestock, identifying the causes of infertility, and stem cell application. Meanwhile, the problem of nucleic acid denaturation observed during embryo development is yet to be resolved. This study was set out to analyze the nucleic acid denaturation during the development of in vitro embryos.Materials and Methods:Using an in-vitro fertilization-embryo in porcine, the cell development and apoptosis were evaluated by adding rapamycin by concentration to the TCM-199 containing 10% FBS or 10% porcine follicle fluid (pFF). Real-time PCR, zymography, DNA fragment, Western blot, and immunofluorescence analysis were also carried out to determine the development rate of inner cell mass in the in-vitro fertilization-embryo.Results:The findings indicated that the addition of rapamycin to the 10% pFF group during in vitro maturation led to an increase in the rates of cleavage and blastocyst development and the expression of active matrix metallopeptidase (MMP-9), while nucleic acid denaturation was suppressed. In other words, the addition of rapamycin was found to increase the expression of MMP-2 in the inner cell mass and trophoblast, while it inhibited apoptosis.Conclusion:The addition of rapamycin influences the regulation of apoptosis and MMPs, and based on this, it is presumed to have a positive effect on blastocyst development.

Bioelectrical Impedance Analysis for Monitoring Fluid and Body Cell Mass Changes in Patients Undergoing Cardiopulmonary Bypass.

ObjectiveTo evaluate preoperative and postoperative body fluid distribution with a bioelectrical impedance analyzer in patients undergoing cardiopulmonary bypass.MethodsFifteen adult patients undergoing cardiopulmonary bypass were included in this study. Total body fluid changes, basal metabolism rates, body fat masses, lean body masses, and total cell masses were recorded. The patients’ values were measured before anesthesia, after anesthesia, after sternotomy, at the 5th, 30th, and 60th minutes of cardiopulmonary bypass, and on the 1st, 3rd, and 5th postoperative days. All values were compared with preoperative values.ResultsTotal body fluid changed significantly after cardiopulmonary bypass (P<0.01). Metabolic velocity significantly changed compared to preoperative measurements (P<0.05). Fat mass and lean body mass also changed significantly. Body mass index and phase angle did not change significantly (P>0.05).ConclusionChanges in body fluids during and after cardiopulmonary bypass are inevitable. The increase in total body weight shows that this fluid load shifts to the extracellular space during bypass and the fluid load in this area passes into the intravascular area in the early postoperative period. This may cause edema and dysfunction in the major organs. Therefore, the fluid balance should be adjusted very carefully, especially during the bypass phase and the early postoperative period.

Inflating bacterial cells by increased protein synthesis.

Understanding how the homeostasis of cellular size and composition is accomplished by different organisms is an outstanding challenge in biology. For exponentially growing Escherichia coli cells, it is long known that the size of cells exhibits a strong positive relation with their growth rates in different nutrient conditions. Here, we characterized cell sizes in a set of orthogonal growth limitations. We report that cell size and mass exhibit positive or negative dependences with growth rate depending on the growth limitation applied. In particular, synthesizing large amounts of “useless” proteins led to an inversion of the canonical, positive relation, with slow growing cells enlarged 7- to 8-fold compared to cells growing at similar rates under nutrient limitation. Strikingly, this increase in cell size was accompanied by a 3- to 4-fold increase in cellular DNA content at slow growth, reaching up to an amount equivalent to ∼8 chromosomes per cell. Despite drastic changes in cell mass and macromolecular composition, cellular dry mass density remained constant. Our findings reveal an important role of protein synthesis in cell division control.

Quantifying Biomass Changes of Single CD8+ T Cells during Antigen Specific Cytotoxicity

Existing approaches that quantify cytotoxic T cell responses rely on bulk or surrogate measurements which impede the direct identification of single activated T cells of interest. Single cell microscopy or flow cytometry methodologies typically rely on fluorescent labeling, which limits applicability to primary cells such as human derived T lymphocytes. Here, we introduce a quantitative method to track single T lymphocyte mediated cytotoxic events within a mixed population of cells using live cell interferometry (LCI), a label-free microscopy technique that maintains cell viability. LCI quantifies the mass distribution within individual cells by measuring the phase shift caused by the interaction of light with intracellular biomass. Using LCI, we imaged cytotoxic T cells killing cognate target cells. In addition to a characteristic target cell mass decrease of 20–60% over 1–4 h following attack by a T cell, there was a significant 4-fold increase in T cell mass accumulation rate at the start of the cytotoxic event and a 2–3 fold increase in T cell mass relative to the mass of unresponsive T cells. Direct, label-free measurement of CD8+ T and target cell mass changes provides a kinetic, quantitative assessment of T cell activation and a relatively rapid approach to identify specific, activated patient-derived T cells for applications in cancer immunotherapy.

Rapidly quantifying drug sensitivity of dispersed and clumped breast cancer cells by mass profiling

Live cell mass profiling is a promising new approach for rapidly quantifying responses to therapeutic agents through picogram-scale changes in cell mass over time. A significant barrier in mass profiling is the inability of existing methods to handle pleomorphic cellular clusters and clumps, which are more commonly present in patient-derived samples or tissue cultures than are isolated single cells. Here we demonstrate automated Live Cell Interferometry (LCI) as a rapid and accurate quantifier of the sensitivity of single cell and colony-forming human breast cancer cell lines to the HER2-directed monoclonal antibody, trastuzumab (Herceptin). The relative sensitivities of small samples (<500 cells) of four breast cancer cell lines were determined tens-to-hundreds of times faster than is possible with traditional proliferation assays. These LCI advances in clustered sample assessment and speed open up the possibility for therapeutic response testing of patient-derived solid tumor samples, which are viable only for short periods ex vivo and likely to be in the form of cell aggregates and clusters.

Elicitation of Trigonelline and 4-Hydroxyisoleucine with Hypoglycemic Activity in Cell Suspension Cultures of Trigonella foenum graecum L

Cell suspension cultures of Trigonella foenum graecum L. (fenugreek) were initiated from the cotyledon portions of sterile germinated seeds and maintained on MS medium supplemented with 2, 4-dichlorophenoxy acetic acid (2, 4-D) (1mg/l), kinetin (0.1 mg/l) and sucrose (5%). The changes in cell mass and both trigonelline and 4- hydroxyisoleucine content were followed between days zero and 12. The linear increase in fresh weight was found to be parallel to both trigonelline and 4-hydroxyisoleucine production. Cell suspension cultures treated with 100 μM methyl jasmonate (MJ) for 24 hours showed a noticeable increase in the level of trigonelline and 4-hydroxyisoleucine. The marked improvement in the histological and electron microscopically pictures of pancreas of STZ-diabetic rats fed with extract of cells treated with MJ is coincided with more effective and significant hypoglycemic activity than that for seeds extract. The extract of cultured cells treated with MJ lowered blood glucose from 284 ± 7.4 to 123 ± 8.1 units and increased the insulin level from 4.42 ± 0.23 μU/ml to a high level 8.33 ± 0.41 μU/ml.

A glimpse at tumor genome evolution

Next-generation DNA sequencing has dramatically affected cancer genomics efforts in several important ways. Although whole genome sequencing remains an analytical challenge, such efforts are yielding data that elucidate the myriad ways in which a genome can be influenced by single point mutations, focused insertions or deletions, and large structural alterations. In addition to cataloguing somatic alterations, various correlation analyses are indicating the genes whose alterations most profoundly determine patient outcomes, patient responses to therapeutics and other important aspects of disease biology. We have recently begun exploring how the digital nature of next-generation sequencing reads allows important information about tumor cell genomic heterogeneity to be inferred, revealing the earliest mutations and how the composition of the tumor cell mass changes over time under the influence of stressors such as chemotherapy.

Life and death in the atherosclerotic plaque

Changes in cell mass in atherosclerosis represent changes in cell division, cell death and migration/emigration, all of which may be occurring simultaneously in different cell types at different times and in different regions of the plaque. This makes measurement of these individual processes and measurement of overall cell kinetics in atherosclerosis difficult, with the challenges and shortfalls only recently becoming apparent. This review will outline the problems associated with assaying cell proliferation and cell death, and how these processes relate to changes in overall cell kinetics and measurement of biological age. Cell division and cell death have historically been assayed as frequencies of specific processes, with at times ill-defined and nonspecific markers. More recent studies have moved towards cumulative assays that can measure overall rates over time, resulting in a 'biological' age or replication history of a tissue or cell. The complexity of processes involved in assaying changes in cell kinetics in atherosclerosis mean that we must move towards cumulative assays of cell proliferation, cell death and senescence that can be measured in the time frames over which atherosclerosis occurs, and for studies that selectively manipulate one of these processes in a single-cell type without affecting other processes.

Multifrequency bioelectrical impedance analysis and bioimpedance spectroscopy for monitoring fluid and body cell mass changes after gastric bypass surgery

There is a growing need for clinically applicable body composition assessment tools for extremely obese individuals. The objective of this research was to evaluate several bioimpedance techniques for monitoring changes in fluid, particularly intracellular water (reflecting body cell mass) after bariatric surgery. Fifteen extremely obese women (body mass index: 48.9+/-7.0 kg/m(2); age: 48+/-9 years) were assessed before (baseline; T1), and approximately 6 weeks after gastric bypass surgery (T2) by several multifrequency bioelectrical impedance analysis approaches (MFBIA; QuadScan 4000), a bioimpedance spectroscopy device (BIS; Hydra 4200), and multiple dilution. BIS provided intracellular water estimates that were comparable to criterion, based on mean comparisons, at both time points (T1: criterion: 24.2+/-3.1L, BIS: 24.0+/-3.7 L; T2: criterion: 20.6+/-3.7 L, BIS: 19.7+/-3.2L). MFBIA (with Deurenberg equations) provided comparable measures to criterion only at T2 (criterion: 20.3+/-3.7L, MFBIA: 20.6+/-2.7 L). Both MFBIA (with QuadScan proprietary equations) and BIS produced estimates of intracellular water change that were comparable to dilution. There was substantial variability in individual volume measures. Although MFBIA and BIS hold promise as convenient techniques for assessing fluid changes, individual variability in measurements makes them impractical for assessment of extremely obese patients in the clinical setting.

Influence of W-7, a calmodulin antagonist on phospholipid biosynthesis in Candida albicans.

This study was undertaken to investigate the role of calmodulin in phospholipid biosynthesis in Candida albicans using W-7, a calmodulin antagonist. Cells were grown as shake cultures in the absence and presence of W-7 at different concentrations. Changes in cell mass, phospholipid content and incorporation of labelled precursor into phospholipid and activities of respective enzymes have been studied. Decreased incorporation of labelled acetate into total lipids and phospholipids was observed in the presence of 40 microm of W-7 which was not as a consequence of altered growth of Candida in the presence of calmodulin antagonist. Further, a significant decrease in the levels of calmodulin and CaM dependent protein kinase activity was observed in cells grown with different concentrations of W-7. This was accompanied by decreased/increased activity of phosphatidic acid phosphatase and phospholipase A, respectively in W-7 grown cells as compared to controls. These findings suggest definite involvement of calmodulin in the regulation of phospholipid metabolism in Candida albicans.

Growth and enumeration of the meat spoilage bacterium Brochothrix thermosphacta

Brochothrix thermosphacta is a common meat spoilage bacterium. The morphology of this bacterium changes from coccobacilli and short rods to chains during growth, which may give a false estimation in numbers using some enumeration techniques. Methods for the quantification of this bacterium have been compared. Turbidimetric readings showed good agreement with cell dry weight indicating that the former provides a good measure of the change in cell mass during growth. The turbidimetric method also correlated well with bacterial numbers determined by plate counts, flow cytometry and manual counts (by microscope) over a limited range of 10 7−10 9 cells/ml. Flow cytometry and manual counts gave a linear relationship over a wider range of 10 5–10 9 cells/ml. The sensitivity of analysis, growth rates and lag time attained using these methods were also compared. As a consequence of changes in bacterial cell size during growth, turbidimetry over-estimated the growth rate. The plate count method proved unable to detect the difference between bacteria existing as chains or single cells. The sensitivity of analysis and the calculated growth related parameters were similar for flow cytometry and manual counts. This suggests that flow cytometry is capable of counting individual cells in a chain. Further investigation showed that passage of B. thermosphacta cells through the flow cytometer resulted in the breakage of chains into single cells. The reliability, low error and rapidity of this technique make it attractive for bacterial enumeration, something which has been demonstrated using B. thermosphacta, a bacterium which exhibits complex morphologies.

Neogenesis vs. apoptosis As main components of pancreatic beta cell ass changes in glucose-infused normal and mildly diabetic adult rats.

We have investigated in adult rats made mildly diabetic by a low dose of streptozotocin (35 mg/kg; STZ rats) and in nondiabetic rats (ND rats) the mechanisms leading to adaptive changes in the beta cell mass, during glucose infusion and several days after stopping infusion. As early as 24 h of glucose infusion, the beta cell mass was maximally increased in ND and STZ rats. In both groups, this increase was due mainly to a rapid activation of neogenesis of new endocrine cells rather than to an increase in beta cell proliferation. Seven days after stopping glucose infusion, the beta cell mass returned to basal values in both groups as a result of stimulation of beta cell apoptosis and a decrease in beta cell replication rate. In glucose-infused ND rats, changes in the beta cell mass were correlated to insulin secretion, whereas in STZ rats, insulin secretion in response to glucose was still impaired whatever the beta cell mass. In conclusion, the data stress the impressive plasticity of the endocrine pancreas of adult rats. They also show that changes in beta cell mass in ND and STZ rats resulted from a disruption in the balance between neogenesis and apoptosis.

Cellular Adhesion and Spreading of Endothelial Cells Monitored in Real Time Using the Quartz Crystal Microbalance

AbstractWe have applied the Quartz Crystal Microbalance (QCM) technique to continuously record the processes of endothelial cell (EC) adhesion, spreading and cellular mass distribution changes during initial cell to surface contact and homeostatic attachment. ECs (50,000) were layered onto a set volume of media in the QCM device and simultaneously in a mock cell used for photomicroscopy. As cells were observed in the mock cell device to contact and attach to the surface over 45-55 min, we measured in the QCM device a continuous decrease in frequency and continuous increase in resistance, achieving a maximum at about one hr (1400 Ω frequency change and 1400 Ω motional resistance change). These frequency and resistance values stabilized over the next 24 hrs and were unchanged out to 72 hr by QCM measurement (to ∼700 Hz, ∼700 Ω), as the cells were observed to spread in the mock device. Both bovine aortic (BAE) and bovine capillary (BCE) endothelial cells were studied and found to exhibit similar behavior. These studies demonstrate that QCM can be used to detect continuous changes in cell mass and viscoelastic behavior.

Effects of oxygen supply on yeast growth and metabolism in continuous fermentation

The yield changes in cell mass and metabolites with changes in the oxygen supply rate were investigated in continuous ethanol fermentation. With increases in oxygen concentration in the purging gas from 5.3 to 39.3 %, the specific oxygen uptake rate ( qO 2) increased from 0.158 to 1.24 mmol/g/h. With this change, cell mass increased from 13.2 to 14.9 g/ l and glycerol decreased from 4.8 to 0.99 g/ l, although little change in ethanol yield was observed. At a higher oxygen concentration and/or at a lower respiratory quotient (RQ), glycerol disappeared, acetaldehyde, acetoin and 2,3-butanediol increased, and ethanol started to decrease. The yields of iso-butylalcohol and iso-amylalcohol also increased with increases in the oxygen supply rate when RQ was lower than approximately 10. Reduction in the redox balance (NADH/NAD) in the cells by qO 2, appeared to reduce initially the rate of glycerol-3-phosphate formation and next the rate of ethanol formation, resulting in the accumulation of acetaldehyde and formation of 2,3-butanediol through acetoin. Fatty acid composition changed with changes in the oxygen supply rate. The value for unsaturation, Δ mol −1, increased from 0.745 to 0.836 with the increase in qO 2 from 0.158 to 1.79 mmol/g/h. Increases in oleic acid (C18:1) and decreases in palmitic acid (C16:0) were the major changes with the increases in Δ mol −1.

Differentiation of the inner cell mass of the baboon blastocyst

During the blastocyst stage of development in the baboon, the inner cell mass changes from an irregular accumulation of cells within the cavity of the blastocyst to a disk at one side of the blastocyst and finally to a spherical mass of epiblast cells exhibiting a distinct polarity. The cells that will become the primitive endoderm are first seen as flattened but undifferentiated cells on the cavity side of the disk-shaped inner cell mass. After endoderm cells develop their typical cytological characteristics, they extend well beyond the inner cell mass to form parietal endoderm. A basal lamina develops associated with the epiblast cells and mural trophoblast, but not with either parietal or visceral endoderm. Cytological differentiation of inner cell mass cells includes increased numbers of polyribosomes and a change in mitochondria from long, convoluted structures to short, more typical shapes. Evidence that epiblast is polarized is seen by the late zonal blastocyst stage. Apical junctional complexes develop within the center of the epiblast. These junctions presage the development of the potential amniotic cavity. Large vacuoles containing cell debris, some of which contain nuclear fragments, are present at all stages. Extensive cell death occurs during growth of the blastocyst, but the pattern appears to be random and products of cell death are readily phagocytized by adjacent cells.

Growth Hormone and Body Composition

Through its anabolic, lipolytic and antinatriuretic actions, GH has profound effects on body composition. In untreated acromegaly, body weight, body cell mass and extracellular water are increased simultaneously with a decrease of body fat. After successful treatment, extracellular water and body fat normalize, but cell mass remains high. The changes in cell mass, body fat and extracellular water observed in acromegaly suggest different dose-response relationships between GH and these parameters. The relationship between GH concentration and the lipolytic actions of GH is more linear, while the relationship between GH and excess extracellular water is more curvilinear. The sodium-retaining effect of GH seems to be mediated by stimulation of the Na(+)-K+ pump. At higher GH levels, the pump activity is counteracted by an alleged sodium transport inhibitor. In GH-deficient children, GH treatment is followed by rapid loss of adipose tissue and muscular gain. The influence of GH on body composition in GH-deficient adults has recently received attention. Compared to normal subjects, these patients are overweight and have decreased cell mass. Replacement treatment with GH restores body composition towards normal.

Effects of increased cell mass and altered gene dosage on the timing of initiation of macronuclear DNA synthesis in Paramecium tetraurelia: Implications for cell cycle regulation

In Paramecium, cell mass and macronuclear DNA content can vary substantially, and both variables affect the timing of initiation of macronuclear DNA synthesis. Cells normally begin macronuclear DNA synthesis at 0.25 in the cell cycle when the mean cell mass is about 119% of the initial value. Gene mutations were used to alter cell size by temporarily blocking cell cycle progression and to change DNA content by altering the segregation pattern of macronuclear material to daughter nuclei at fission. Changes in cell mass or macronuclear DNA content imposed at fission or in the subsequent G1 interval do not affect the timing of initiation of DNA synthesis in that cell cycle, but do affect the timing of initiation of DNA synthesis in the subsequent cell cycle. The progeny of cells with lower than average macronuclear DNA content tend to initiate DNA synthesis earlier than other cells. The G1 interval is proportionally shortened when initial cell mass is greater than normal, and no measurable G1 interval is present when initial cell mass equals or exceeds the normal cell mass present at initiation of DNA synthesis. These results suggest that the timing of initiation of DNA synthesis is established during the preceding cell cycle and that the ‘timer’ mechanism is not significantly affected by either drastic changes in gene dosage or gene concentration during the G1 interval.

A clinical staging system for multiple myeloma. Correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival.

The presenting clinical features of 71 patients with multiple myeloma were correlated with myeloma cell mass (myeloma cells X 10(12)/m2 of body surface area) determined from measurements of monoclonal immunoglobulin (M-component) synthesis and metabolism. Bivariate correlation and multivariate regression analyses showed that myeloma cell mass could be accurately predicted from A) extent of bone lesions, B) hemoglobin level, C) serum calcium level, and D) M-component levels in serum and urine. Analyses of response to chemotherapy and survival indicated significant correlation with measured myeloma cell burden. The results were synthesized to produce a very reliable and useful clinical staging system with three tumor cell mass levels (Table 7). For clinical research purposes, multivariate regression equations were developed to predict optimally the exact myeloma cell mass. Thus, initial staging can be quantitatively related to followup using tumor cell mass changes calculated from changes in M-component production. Use of the clinical staging system sould provide better initial assessment and followup of individual patients, and should lead to improved study design and analysis in large clinical trials of therapy for multiple myeloma.