Cell shape-mediated growth control of lens epithelial cells grown in culture.
Explore the source record for details and available documents.
Animals↗
SEARCH · Search PubMed
Results for “Cell Shape”
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Interleukin-1 induces major phenotypic changes in human skin microvascular endothelial cells.
To determine the role of the pleiotropic cytokine interleukin-1 (IL-1) on the activation of endothelial cells during inflammation and angiogenesis, pure populations of human dermal microvascular endothelial cells (HDMEC) were obtained by immunoaffinity purification using Ulex europaeus agglutinin-1 and platelet endothelial cell adhesion molecule-1 (PECAM-1) antibody. Exposure of HDMEC to IL-1beta induced morphologic and physiologic changes characterized by 1) phenotypic modulation of endothelial cells from epithelioid to spindle-shaped cells accompanied by reorganization of vimentin filaments; 2) gradual decrease to a complete absence of the endothelial cell markers von Willebrand factor (vWf) and PECAM-1; and 3) increased capability to form tubule-like structures when overlaid with collagen gels. The IL-1 effect on cell morphology, growth, and decrease of endothelial cell antigens was potentiated by basic fibroblast growth factor (bFGF). Similar results were observed in mitotically arrested gamma-irradiated cells demonstrating that the spindle-shaped cells observed after IL-1 stimulation were derived from epithelioid endothelial cells and that DNA synthesis was not required to effect these changes. Immunostaining with an antibody specific for human fibroblasts was negative and further confirmed the endothelial cell origin of the spindle-shaped cells. These data demonstrate that IL-1 can induce phenotypic changes in HDMEC from epithelioid to spindle-shaped, mesenchymal-like cells, that these cells are more susceptible to stimulation by bFGF, and that they lose biochemical and functional properties characteristic of epithelioid HDMEC.
Cell Division↗
[The effect of trophoblast-specific beta 1-glycoprotein and oncoprecipitin A on the growth and morphology of HeLa-M tumor cells].
Pregnancy-specific beta 1-glycoprotein (PS-1), one of a large family in oncofetal antigens, and oncoprecipitin A, a specific glycoprotein isolated from ascidians, have been shown to reduce cell proliferative activity in HeLa-M cells but almost not to change RNA synthesis. Using scanning electron microscopy, distinct surface transductions in the studied cells were demonstrated. After the incubation of cells with oncoprecipitin A, cell shape alteration and intensive cell spreading were observed. The treatment of tumor cells with PS-1 changed cell shape and essentially reduced cell contacts, as compared to control cells. The changes in cell surface and shape correlated with essential reorganization of actin microfilaments. The use of substances influencing the growth and adhesive characteristics of tumor cells may help in understanding mechanisms of cell transformation.
Animals↗
Histomorphological and proliferative characterization of developing periosteal neochondrocytes in vitro.
Periosteal chondrogenesis is relevant to cartilage repair and fracture healing. Cell proliferation is a limiting factor of cartilage production. We used an in vitro organ culture model to test the hypothesis that proliferative activity correlates with cell morphology. One hundred and four periosteal explants from 26 two-month old New Zealand rabbits were cultured for up to 42 days. They were analyzed histomorphologically, and immunohistochemically with proliferative cell nuclear antigen (PCNA). The periosteal neocartilage displayed a consistent zonal pattern of chondrocyte cell shapes. The flat cell zone from day 7 to 21, consisted of uniform-sized small spindle-shaped cells. The round cell zone, which appeared on day 14, consisted of variable-sized round cells averaging 510 +/- 250 microm2 in area. They were subdivided into small round (<510 microm2) and large round cells (>510 microm2). The proliferative index was highest in the small round cell group (32 +/- 6%), intermediate in the flat cell group (27 +/- 6%), and lowest in the large round cell group (20 +/- 7%) (P < 0.001). Furthermore, the proliferative indices in the round cell group were inversely proportional to cell size. Therefore, (1) there is a sequential progression of cell morphology during periosteal chondrogenesis, (2) cell differentiation is arrested prior to terminal differentiation for some cells and not for others, and (3) proliferative activity is strongly related to cell morphology. This organ culture model provides us with opportunities to study the regulation of terminal chondrocyte differentiation and the control of cell proliferation. This will contribute to our understanding of cartilage repair, fracture healing and growth plate physiology.
Animals↗
Functional analysis of Cdc42 in actin filament assembly, epithelial morphogenesis, and cell signaling during Drosophila development.
Cdc42, a member of the Rho family of GTP binding proteins, functions in the formation of polarized actin structures, in elongation of cell shape, and in cell signaling. Although genetic mutations previously have not been available in multicellular organisms, studies have attempted to discern Cdc42 functions in organisms, including Drosophila, using dominant active or interfering alleles. Here, for the first time, we examine the functions of Cdc42 in developing tissues using loss-of-function mutations in the Drosophila Cdc42 gene. We find that Cdc42(-) epithelial cells fail to elongate into a columnar cell shape and cannot maintain a monolayered epithelial structure. In contrast to previous studies, we find no requirement for Cdc42 in cell division or in activation of the Jun N-terminal kinase pathway. In addition, Cdc42 function is not required for cytoplasmic actin filament assembly in the nurse cells during oogenesis, although it may facilitate this process. Furthermore, our results indicate that Cdc42 plays a role in intercellular interactions between the germ line and the somatic follicle cells. These results confirm the role of Cdc42 in actin filament assembly and provide new insights into its functions in epithelial morphogenesis and regulating intercellular signaling events.
Actins↗
Cell membrane shape control--effects of chloromethyl ketone peptides.
The shape of the human erythrocyte is normally maintained in vivo as a biconcave disc for 120 days. In vitro, the cell shape can be altered readily by amphipathic compounds; however, given time and an energy source, the cells can recover the discoid morphology. An active shape control mechanism is postulated to regulate erythrocyte shape. The shape recovery process is a necessary element in reversing perturbations of shape and is basic to our understanding of how membrane shape is altered. We report here that the process of shape recovery from crenation is dramatically accelerated upon pretreatment of the cells with micromolar (20-100 microM) concentrations of chloromethyl ketone peptides [such as N-alpha-tosyl-L-phenylalanine-chloromethyl ketone (tos-pheCH2Cl)]. Such pretreatments do not appear to affect cellular viability, as judged by their normal biconcave disc shape, their sensitivity to crenators, their lactic acid production, or the ATP-dependent shape change of the purified membranes. Treatment with high concentrations of tos-pheCH2Cl does cause normal cells to become stomatocytic by an energy-requiring process, i.e., it requires glucose, incubation at 37 degrees C, and will not occur in ATP-depleted cells. We suggest that the chloromethyl ketone peptides affect a metabolic process that is associated with the hexose monophosphate (HMP) shunt. Through the alteration of the HMP shunt metabolism, they modify an active stomatocytic process in the erythrocyte that can correct for the perturbation caused by crenators. Implications of these findings for analogous phenomena in cultured cells are discussed.
2,4-Dinitrophenol↗
Real-time imaging of cell-cell adherens junctions reveals that Drosophila mesoderm invagination begins with two phases of apical constriction of cells.
Invagination of the epithelial cell sheet of the prospective mesoderm in Drosophila gastrulation is a well-studied, relatively simple morphogenetic event that results from dynamic cell shape changes and cell movements. However, these cell behaviors have not been followed at a sufficiently short time resolution. We examined mesoderm invagination in living wild-type embryos by real-time imaging of fluorescently labeled cell-cell adherens junctions, which are located at the apical zones of cell-cell contact. Low-light fluorescence video microscopy directly visualized the onset and progression of invagination. In an initial period of approximately 2 minutes, cells around the ventral midline reduced their apical surface areas slowly in a rather synchronous manner. Next, the central and more lateral cells stochastically accelerated or initiated their apical constriction, giving rise to random arrangements of cells with small and relatively large apices. Thus, we found that mesoderm invagination began with slow synchronous and subsequent fast stochastic phases of cell apex constriction. Furthermore, we showed that the mesoderm invagination of folded gastrulation mutant embryos lacked the normal two constriction phases, and instead began with asynchronous, feeble cell shape changes. Our observations suggested that Folded gastrulation-mediated signaling enabled synchronous activation of the contractile cortex, causing competition among the individual mesodermal cells for apical constriction. Movies available on-line: http://www.biologists.com/JCS/movies/jcs2073.html
Animals↗
Electrophysiological analysis of the negative chronotropic effect of endothelin-1 in rabbit sinoatrial node cells.
1. Electrophysiological effects of endothelin-1 (ET-1) were studied in rabbit sinoatrial node (SAN) using conventional microelectrode and whole-cell voltage and current recordings. 2. In rabbit SAN, RT-PCR detected ET(A) endothelin receptor mRNA. ET-1 (100 nM) increased the cycle length of action potentials (APs) from 305 +/- 15 to 388 +/- 25 ms; this effect was antagonised by the ET(A) receptor-selective antagonist BQ-123 (1 microM). ET-1 increased AP duration (APD50) by 22%, depolarised the maximum diastolic potential (MDP) from -59 +/- 1 to -53 +/- 2 mV, shifted the take-off potential by +5 mV and decreased the pacemaker potential (PMP) slope by 15%. Under exactly the same experimental conditions, ET-1 caused a positive chronotropic effect in guinea-pig SAN with a decrease of 13% in APD50, a shift of -4 mV in the take-off potential and an increase of 8% in the PMP slope. 3. Rabbit SAN exhibited two major cell types, distinguished both by their appearances and by their electrophysiological responses to ET-1. Whereas the spontaneous pacing rate and the PMP slope were similarly decreased by ET-1 (10 nM) in both cell types, ET-1 depolarised MDP from -67 +/- 1 to -62 +/- 4 mV in spindle-shaped cells but hyperpolarised it from -73 +/- 1 to -81 +/- 3 mV in rod-shaped cells. ET-1 decreased APD50 by 8 and 52% and shifted the take-off potential by +5 and -9 mV in spindle- and rod-shaped cells, respectively. 4. ET-1 decreased the high-threshold calcium current (I(CaL)) by about 50% in both cell types, without affecting its voltage dependence, and decreased the delayed rectifier K+ current (I(K)) with significant shifts (of +4.7 and +14.0 mV in spindle- and rod-shaped cells, respectively) in its voltage dependence. It was exclusively in rod-shaped cells that ET-1 activated a sizeable amount of time-independent inward-rectifying current. 5. The hyperpolarisation-activated current (I(f)), observed exclusively in spindle-shaped cells, was significantly increased by ET-1 at membrane potentials between -74.7 and -84.7 mV whereas it was significantly decreased at more negative potentials. ET-1 significantly decreased the slope of the current-voltage (I-V) relation of the I(f) tail without changing its half-maximum voltage. 6. The overall negative chronotropic influence of ET-1 on the whole rabbit SAN is interpreted as resulting from the integration of its different actions on spindle- and rod-shaped SAN cells through electrotonic interaction.
Action Potentials↗
SPARC-null mice exhibit increased adiposity without significant differences in overall body weight.
Secreted protein acidic and rich in cysteine/osteonectin/BM-40 (SPARC) is a matrix-associated protein that elicits changes in cell shape, inhibits cell-cycle progression, and influences the synthesis of extracellular matrix (ECM). The absence of SPARC in mice gives rise to aberrations in the structure and composition of the ECM that result in generation of cataracts, development of severe osteopenia, and accelerated closure of dermal wounds. In this report we show that SPARC-null mice have greater deposits of s.c. fat and larger epididymal fat pads in comparison with wild-type mice. Similar to earlier studies of SPARC-null dermis, we observed a reduction in collagen I in SPARC-null fat pads in comparison with wild-type. Although elevated levels of serum leptin were observed in SPARC-null mice, their overall body weights were not significantly different from those of wild-type counterparts. The diameters of adipocytes from SPARC-null versus wild-type epididymal fat pads were 252 +/- 61 and 161 +/- 33 microm (means +/- SD), respectively, and there was an increase in adipocyte number within SPARC-null fat pads in comparison with wild-type pads. Thus the absence of SPARC appears to result in an increase in the size of individual adipocytes as well as an increase in the number of adipocytes per fat pad. In fat pads isolated from wild-type mice, SPARC mRNA was associated with both the stromal/vascular and adipocyte fractions. We propose that SPARC limits the accumulation of adipose tissue in mice in part through its demonstrated effects on the regulation of cell shape and production of ECM.
Adipose Tissue↗
Teardrop-shaped red cells in autoimmune hemolytic anemia.
The presence of teardrop-shaped red cells in peripheral blood has traditionally been felt to reflect altered marrow architecture, namely myelofibrosis. We evaluated two patients with splenomegaly, moderately severe hemolytic anemia due to warm-reactive IgG anti-red cell autoantibody, and bone marrow erythroid hyperplasia without myelofibrosis. A striking predominance of teardrop-shaped red cells was noted upon examination of their blood films. Removal of a spleen containing extramedullary hematopoiesis in one and resolution of splenomegaly in the other were accompanied by disappearance of these cells. Our observations support a role for the spleen and for extramedullary hematopoiesis in the pathogenesis of this distinctive red cell morphologic abnormality.
Anemia, Hemolytic, Autoimmune↗
Three-dimensional cytoarchitecture of the media of arteriovenous anastomoses in the rabbit ear.
Arteriovenous anastomoses in the rabbit ear were examined with scanning electron microscopy to elucidate the structural differentiation of the media of the shunt. Arterial, intermediate, and venous segments in the shunt and two layers of the media in the intermediate segment were differentiated based on cell shape and cell organization. In the arterial segment, smooth muscle cells were spindle-shaped, either elongated or short, with a few branches, and were arranged circularly or diagonally with respect to the vessel's long axis. There were also stellate muscle cells with radiating processes. In the intermediate segment, the smooth muscle cells of the outer layer of the media were also arranged circularly and resembled the elongated cells in the arterial segments, but they were more irregular in shape and had more processes than those of the arterial segment. The epithelioid cells of the inner layer of the media were oval or polygonal and oriented irregularly with respect to the vessel's long axis, clustering to form longitudinal plicae. The smooth muscle cells of the venous segment were flat with many lateral processes and formed a thin, discontinuous layer. The smooth muscle cells in the arterial segment and those of the outer layer of the intermediate segment exhibited a highly rugged surface texture, indicating their strong contractility; the epithelioid cells and the smooth muscle cells in the venous segment exhibited a generally smooth surface, indicating less contractility. The intermediate segments were supplied with a dense nerve plexus. The intermediate segments, therefore, may be actively involved in the regulation of blood flow under neuronal influence.
Animals↗
[Mechanotransduction and tensegrity (I)].
The current review deals with mechanotransduction by means of an architectural model of cell function called tensegrity. This concept was introduced by D. E. Ingber in order to frame more focused mechanisms of mechano-transduction, i.e. different signaling pathways, which are less able to predict global cellular behaviour in response to stress, into a coherent mechano-chemical theory of cell function. Tensegrity structures are made and held up by interconnecting a continuous series of tension elements with a discontinuous series of compression resistant struts, in a simple "stick and string" model. These structures develops an intrinsic stabilizing tension called prestress and reacts by global rearrangements of their configuration to a local action of a mechanical stress. The only requirement of a tensegrity network is that tension is continuous and compression is local. At the cellular level the theory assumes that membrane, nucleus and all the organelles are hard-wired by the insoluble cytoskeletal (CSK) scaffold. More than that, the interconnection between CSK and the extracellular matrix (ECM) provides an efficient mechanical couple responsible for changes in cell shape and movement. Cell shape, in turn, regulates cellular function. Focal adhesion complexes, which mediate the CSK-ECM interaction are viewed as integrative devices for both mechanical signaling and soluble factor-dependent signaling. Furthermore, the tensegral molecular network is considered to be a solid-state regulatory system of all cell functions. The way tensegrity influences molecular mechanics, cellular response tuning and coordinated behaviour of large scale structures are also discussed. Besides its conceptual importance, the tensegrity model has multiple applications, being used in combined approach of cell biology, bioengineering, architecture, and biomechanics in order both to improve cell culture and its subsequent applications and the open the way to a more complex technology of tissular engineering.
Animals↗
Identification of the tumor metastasis suppressor Nm23-H1/Nm23-R1 as a constituent of the centrosome.
Processes like cell proliferation, differentiation, and tumor metastasis require a flexible adaptation of cell shape and cell plasticity. A regulator of cell structure and shape is the centrosome and its associated microtubules. Recently, oncogenes like p53, pRB, and the tumor suppressor BRCA1 have been characterized as members of the centrosome. In this communication, we identified rat Nm23-R1/NDPKbeta, a homologue of the human tumor metastasis suppressor Nm23-H1 and a regulator of cell proliferation and differentiation, as a component of the centrosomal complex. We used confocal laser scanning microscopy on different cell types and biochemical analysis of purified centrosomes to demonstrate that Nm23-R1 is located in the centrosome of dividing and nondividing cells. We also showed that the centrosomal enzyme is catalytically active and able to transfer the gamma-phosphate from a nucleoside triphosphate to a nucleoside diphosphate. In addition, Nm23-R1 coimmunoprecipitated with gamma-tubulin, a core centrosomal protein essential for microtubule nucleation. In addition, human Nm23-R1/-H1 was also shown to be present in the centrosome of different human and rat cell types, demonstrating that the presence of Nm23-H1 homologues in the latter organelle is a general event.
Adenosine Triphosphate↗
Phosphatidylinositol 4,5-bisphosphate functions as a second messenger that regulates cytoskeleton-plasma membrane adhesion.
Binding interactions between the plasma membrane and the cytoskeleton define cell functions such as cell shape, formation of cell processes, cell movement, and endocytosis. Here we use optical tweezers tether force measurements and show that plasma membrane phosphatidylinositol 4,5-bisphosphate (PIP2) acts as a second messenger that regulates the adhesion energy between the cytoskeleton and the plasma membrane. Receptor stimuli that hydrolyze PIP2 lowered adhesion energy, a process that could be mimicked by expressing PH domains that sequester PIP2 or by targeting a 5'-PIP2-phosphatase to the plasma membrane to selectively lower plasma membrane PIP2 concentration. Our study suggests that plasma membrane PIP2 controls dynamic membrane functions and cell shape by locally increasing and decreasing the adhesion between the actin-based cortical cytoskeleton and the plasma membrane.
3T3 Cells↗
Free and polymerized tubulin in cultured bone cells and Chinese hamster ovary cells: the influence of cold and hormones.
Free and polymerized tubulin were measured in bone cells and Chinese hamster ovary (CHO) cells cultured on plastic substrata. Polymerized tubulin was stabilized in a microtubule- stabilizing medium (MSM) containing 50 percent glycerol and separated from free tubulin by centrifugation. Tubulin content was assayed in both fractions by the colchicines- binding assay. The measured degree of polymerization in both bone cells and CHO cells varied with stabilixation conditions. The degree of polymerization in both bone cells and CHO cells varied with stabilization conditions. The degree of polymerization in both bone cells and CHO cells varied with stabilization conditions. The degree of polymerization in attached cells was found to increase up to 73 percent during the first 20 min after addition of the MSM at 24 degrees C, and remained constant thereafter. Stabilization of 0 degrees C resulted in a decrease down to 62 percent in the degree of constant thereafter. Stabilization at 0 degrees C resulted in a decrease down to 62 percent in the degree of polymerization during the first 20 min after addition of the MSM at 24 degrees C, and remained constant thereafter. Confluent bone cells maintained at 0 degrees C for 1 h before stabilization contained significantly less polymerized tubulin than control cells kept at 37 degrees C using stabilization both at 0 degrees C and at 24 degrees C. Changes in bone cell morphology induced by incubation of cells with prostaglandin E(1) or E(2), parthyroid hormone, and dibutyryl cyclic AMP were not associated with a change in the degree of tubulin polymerization. This was confirmed morphologically by immunofluorescence using affinity-purified tubulin antibodies: microtubules in hormone- treated cells were not noticeably reorganized when compared to microtubule organization in control cells. They were, however, squeezed closer together in cellular pseudopods due to the altered cell shape. This altered cell shape appears to be correlated with disorganization of the microfilament system, since microfilaments, detected using affinity-purified actin antibodies, did alter drastically their appearance and distribution after hormone addition.
Alprostadil↗
Number and distribution of interstitial cells lining the epidermis of normal human skin from different anatomical locations.
A study was conducted to determine the number and distribution of interstitial cells lining the epidermis of normal human skin from various anatomical locations. Five to seven normal human skin specimens per each anatomical site were collected from surgical specimens, mostly with pigmented nevi. Ten anatomical locations were classified; and a total of 65 normal human skin samples were evaluated. The number of interstitial cells lining the epidermis was quantified under light microscopy using a computer-assisted image analyzer. Two types of interstitial cells were recognized beneath the dermo-epidermal junction of normal human skin: cells containing oval nuclei and spindle-shaped cells containing elongated nuclei. As for the number of oval cells, no significant difference was found among the anatomical locations. In contrast, significantly greater numbers of spindle-shaped cells were found in the palm (4.11 + 1.24; p < 0.01), sole (3.52 + 0.83; p < 0.001) and buttock (2.52 + 0.49; p < 0.01), compared with those in the anterior trunk (0.60 + 0.22). In normal skin of the palm and sole, the number of spindle-shaped cells located beneath the apices of rete ridges (7.35 + 1.56) was significantly greater than along the dermal papillae (1.39 + 0.39, p < 0.01). However, cells containing oval nuclei also predominated beneath the apices of rete ridges, but the difference was not significant. In summary, the present study demonstrated that the number of spindle-shaped cells, quantified by H & E staining, was significantly greater beneath the apices of rete ridges than in dermal papillae. The number was greater in palm and sole skin compared with other samples of normal human skin. This data may relate to the glabrous nature of palm and sole skin.
Antigens, CD34↗
The carboxy terminus of AFAP-110 modulates direct interactions with actin filaments and regulates its ability to alter actin filament integrity and induce lamellipodia formation.
The actin filament-associated protein AFAP-110 is an SH2/SH3 binding partner for Src. AFAP-110 contains several protein-binding motifs in its amino terminus and has been hypothesized to function as an adaptor molecule that could link signaling proteins to actin filaments. Recent studies using deletional mutagenesis demonstrated that AFAP-110 can alter actin filament integrity in SV40 transformed Cos-1 cells. Thus, AFAP-110 may be positioned to modulate the effects of Src upon actin filaments. In this report, we sought to determine whether (a) AFAP-110 could interact with actin filaments directly and (b) deletion mutants could affect actin filament integrity and cell shape in untransformed fibroblast cells. The data demonstrate that the carboxy terminus of AFAP-110 is both necessary and sufficient for actin filament association, in vivo and in vitro. Analysis of the carboxy terminus revealed a mean 40% similarity with other known actin-binding motifs, indicating a mechanism for binding to actin filaments. AFAP-110 can also induce lamellipodia formation. Contiguous with the alpha-helical, actin-binding motif is an alpha-helical, leucine zipper motif. Deletion of the leucine zipper motif (AFAP(Deltalzip)) followed by cellular expression enabled AFAP(Deltalzip) to alter actin filament integrity and cell shape in untransformed cells as evidenced by the induction of lamellipodia formation. We hypothesize that AFAP-110 may be an important signaling protein that can directly modulate changes in actin filament integrity and induce lamellipodia formation.
3T3 Cells↗
The "epiligament" of the rabbit medial collateral ligament: a quantitative morphological study.
The thin layer of connective tissue covering ligaments--the epiligament--has not been well described. The aim of the present study was to define, describe, and quantify the structure of the epiligament of the rabbit medial collateral ligament (MCL) using polarized light, scanning-electron, transmission-electron microscopy, and computerized histomorphometry. Epiligament was composed of woven bundles of collagen fibers, 3 morphologically-distinct cell types (spinous-shaped cells, cuboidal-shaped cells, and fat cells), and a neurovascular network that periodically arborized into the MCL. The areal fraction of vessels was significantly greater in the epiligament than in the MCL. The epiligament was significantly thicker on the superficial surface of the MCL than the deep surface, and the thickness of epiligament changed significantly during skeletal growth. Based on these structural features we speculate that the epiligament serves several important functions including: (1) protecting the MCL against abrasion, (2) supporting the neurovasculature, (3) controlling water and metabolite flux into the epiligament and possibly the MCL, and (4) being a source of extracellular matrix, cells, and vasculature during ligament growth and during ligament healing.
Animals↗