戴建武
组织工程和再生医学
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- 姓名:戴建武
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学术头衔:
博士生导师
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学科领域:
细胞生物学
- 研究兴趣:组织工程和再生医学
戴建武,男,1965年6月出生,安徽宿松人。主要履历及经历:1984-1988 武汉大学生物系,细胞生物学专业,学士;1988-1991 北京医科大学,生物物理专业,硕士;1991-1993 北京医科大学细胞生物学习 讲师;1993-1998 美国DUKE UNIVERSITY细胞生物学 博士;1998-2000 美国HARVARD UNIVERSITY博士后;2000-2003 美国组织工程公司,科学家,副总裁;2003.8- 中国科学院遗传与发育生物学研究所研究员、博士生导师,入选中国科学院“百人计划”。
主要研究领域:研究方向为组织工程和再生医学,主要研究内容包括:1.功能生物材料的研制及其在损伤修复中的应用。2.干细胞的生长,分化调控的研究及其在再生医学中的应用。
2006年中国科学院“百人计划”顺利结题,2006年获中国科学院遗传发育所SCI论文数量最多奖和影响因子累计最高奖,2007年获中国科学院遗传发育所SCI论文数量最多奖。
学术兼职:《遗传学报》第三届编委会,编委;《中华损伤与修复杂志》常务编委;南方医科大学客座教授。
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10
【期刊论文】Membrane Tether Formation from Blebbing Cells
戴建武, Jianwu Dai and Michael P. Sheetz
Biophysical Journal Volume 77 December 1999 3363-3370,-0001,():
-1年11月30日
Membrane tension has been proposed to be important in regulating cell functions such as endocytosis and cell motility. The apparent membrane tension has been calculated from tether forces measured with laser tweezers. Both membrane-cytoskeleton adhesion and membrane tension contribute to the tether force. Separation of the plasma membrane from the cytoskeleton occurs in membrane blebs, which could remove the membrane-cytoskeleton adhesion term. In renal epithelial cells, tether forces are significantly lower on blebs than on membranes that are supported by cytoskeleton. Furthermore, the tether forces are equal on apical and basolateral blebs. In contrast, tether forces from membranes supported by the cytoskeleton are greater in apical than in basolateral regions, which is consistent with the greater apparent cytoskeletal density in the apical region. We suggest that the tether force on blebs primarily contains only the membrane tension term and that the membrane tension may be uniform over the cell surface. Additional support for this hypothesis comes from observations of melanoma cells that spontaneously bleb. In melanoma cells, tether forces on blebs are proportional to the radius of the bleb, and as large blebs form, there are spikes in the tether force in other cell regions. We suggest that an internal osmotic pressure inflates the blebs, and the pressure calculated from the Law of Laplace is similar to independent measurements of intracellular pressures. When the membrane tension term is subtracted from the apparent membrane tension over the cytoskeleton, the membrane-cytoskeleton adhesion term can be estimated. In both cell systems, membranecytoskeleton adhesion was the major factor in generating the tether force.
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【期刊论文】Myosin I Contributes to the Generation of Resting Cortical Tension
戴建武, Jianwu Dai, * H. Ping Ting-Beall, # Robert M. Hochmuth, # Michael P. Sheetz, * and Margaret A. Titus*
Biophysical Journal Volume 77 August 1999 1168-1176,-0001,():
-1年11月30日
The amoeboid myosin I's are required for cellular cortical functions such as pseudopod formation and macropinocytosis, as demonstrated by the finding that Dictyostelium cells overexpressing or lacking one or more of these actin-based motors are defective in these processes. Defects in these processes are concomitant with changes in the actin-filled cortex of various Dictyostelium myosin I mutants. Given that the amoeboid myosin I's possess both actin- and membrane-binding domains, the mutant phenotypes could be due to alterations in the generation and/or regulation of cell cortical tension. This has been directly tested by analyzing mutant Dictyostelium that either lacks or overexpresses various myosin I's, using micropipette aspiration techniques. Dictyostelium cells lacking only one myosin I have normal levels of cortical tension. However, myosin I double mutants have significantly reduced (50%) cortical tension, and those that mildly overexpress an amoeboid myosin I exhibit increased cortical tension. Treatment of either type of mutant with the lectin concanavalin A (ConA) that cross-links surface receptors results in significant increases in cortical tension, suggesting that the contractile activity of these myosin I's is not controlled by this stimulus. These results demonstrate that myosin I's work cooperatively to contribute substantially to the generation of resting cortical tension that is required for efficient cell migration and macropinocytosis.
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【期刊论文】Membrane Tension in Swelling and Shrinking Molluscan Neurons
戴建武, Jianwu Dai, Michael P. Sheetz, Xiaodong Wan, and Catherine E. Morris
The Journal of Neuroscience, September 1, 1998, 18 (17): 6681-6692,-0001,():
-1年11月30日
When neurons undergo dramatic shape and volume changes, how is surface area adjusted appropriately? The membrane tension hypothesis-namely that high tensions favor recruitment of membrane to the surface whereas low tensions favor retrieval-provides a simple conceptual framework for surface area homeostasis. With membrane tension and area in a feedback loop, tension extremes may be averted even during excessive mechanical load variations. We tested this by measuring apparent membrane tension of swelling and shrinking Lymnaea neurons. With hypotonic medium (50%), tension that was calculated from membrane tether forces increased from 0.04 to as much as 0.4 mN/m, although at steady state, swollen-cell tension (0.12 mN/m) exceeded controls only threefold. On reshrinking in isotonic medium, tension reduced to 0.02 mN/m, and at the substratum, membrane invaginated, creating transient vacuolelike dilations. Swelling increased membrane tension with or without BAPTA chelating ytoplasmic Ca2+, but with BAPTA, unmeasurably large (although not lytic) tension surges occurred in approximately two-thirds of neurons. Furthermore, in unarborized neurons voltage-clamped by perforated-patch in 50% medium, membrane capacitance increased 8%, which is indicative of increasing membrane area. The relatively damped swelling–tension responses of Lymnaea neurons (no BAPTA) were consistent with feedback regulation. BAPTA did not alter resting membrane tension, but the large surges during swelling of BAPTA-loaded neurons demonstrated that 50% medium was inherently treacherous and that tension regulation was impaired by subnormal cytoplasmic [Ca2+]. However, neurons did survive tension surges in the absence of Ca2+ signaling. The mechanism to avoid hightension rupture may be the direct tension-driven recruitment of membrane stores.
surface area, mechanosensitive, cell volume, BAPTA, laser tweezers, vacuole-like dilations
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【期刊论文】A Role for Dictyostelium RacE in Cortical Tension and Cleavage Furrow Progression
戴建武, Noel Gerald, * Jianwu Dai, * H. Ping Ting-Beall, ‡ and Arturo De Lozanne*
Published April 20, 1998,-0001,():
-1年11月30日
The small GTPase racE is essential for cytokinesis in Dictyostelium. We found that this require- ment is restricted to cells grown in suspension. When attached to a substrate, racE null cells form an actomyosin contractile ring and complete cytokinesis normally. Nonetheless, racE null cells fail completely in cytokinesis when in suspension. To understand this conditional requirement for racE, we developed a method to observe cytokinesis in suspension. Using this approach, we found that racE null cells attempt cytokinesis in suspension by forming a contractile ring and cleavage furrow. However, the cells form multiple blebs and fail incytokinesis by regression of the cleavage furrow. We believe this phenotype is caused by the extremely low level of cortical tension found in racE null cells com- pared to wild-type cells. The reduced cortical tension of racE null cells is not caused by a decrease in their content of F-actin. Instead, mitotic racE null cells contain abnormal F-actin aggregates. These results suggest that racE is essential for the organization of the cortical cytoskeleton to maintain proper cortical integrity. This function of racE is independent of attachment to a sub- strate, but can be bypassed by other signaling pathways induced by adhesion to a substrate.
The small GTPase racE is essential for cytokinesis in Dictyostelium., We found that this requirement is restricted to cells grown in suspension., When
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【期刊论文】The Secretion-coupled Endocytosis Correlates with Membrane Tension Changes in RBL 2H3 Cells
戴建武, Jianwu Dai, * H. Ping Ting-Beall, ‡ and Michael P. Sheetz *
Published July 1, 1997,-0001,():
-1年11月30日
Stimulated secretion in endocrine cells and neuronal synapses causes a rise in endocytosis rates to recover the added membrane. The endocytic process involves the mechanical deformation of the membrane to produce an invagination. Studies of osmotic swelling effects on endocytosis indicate that the increased surface tension is tightly correlated to a significant decrease of endocytosis. When rat basophilic leukemia (RBL) cells are stimulated to secrete, there is a dramatic drop in the membrane tension and only small changes in membrane bending stiffness. Neither the shape change that normally accompanies secretion nor the binding of ligand without secretion causes a drop in tension. Further, tension decreases within 6 s, preceding shape change and measurable changes in endocytosis. After secretion stops, tension recovers. On the basis of these results we suggest that the physical parameter of membrane tension is a major regulator of endocytic rate in RBL cells. Low tensions would stimulate endocytosis and high tensions would stall the endocytic machinery.
membrane tension • membrane tether • laser tweezers • secretion • endocytosis
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【期刊论文】Deformation and Flow of Membrane into Tethers Extracted from Neuronal Growth Cones
戴建武, Robert M. Hochmuth, * Jin-Yu Shao, * Jianwu Dai, ‡ and Michael P. Sheetz‡
Biophysical Journal Volume 70 January 1996 358-369,-0001,():
-1年11月30日
Membrane tethers are extracted at constant velocity from neuronal growth cones using a force generated by a laser tweezers trap. A thermodynamic analysis shows that as the tether is extended, energy is stored in the tether as bending and adhesion energies and in the cell body as "nonlocal" bending. It is postulated that energy is dissipated by three viscous mechanisms including membrane flow, slip between the two monolayers that form the bilayer, and slip between membrane and cytoskeleton. The analysis predicts and the experiments show a linear relation between tether force and tether velocity. Calculations based on the analytical results and the experimental measurements of a tether radius of ~0.2 μm and a tether force at zero velocity of ~8 pN give a bending modulus for the tether of 2.7×10-19 N-m and an extraordinarily small "apparent surface tension" in the growth cone of 0.003 mN/m, where the apparent surface tension is the sum of the far-field, in-plane tension and the energy of adhesion. Treatments with cytochalasin B and D, ethanol, and nocodazole affect the apparent surface tension but not bending. ATP depletion affects neither, whereas large concentrations of DMSO affect both. Under conditions of flow, data are presented to show that the dominant viscous mechanism comes from the slip that occurs when the membrane flows over the cytoskeleton. ATP depletion and the treatment with DMSO cause a dramatic drop in the effective viscosity. If it is postulated that the slip between membrane and cytoskeleton occurs in a film of water, then this water film has a mean thickness of only ~10 A.
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【期刊论文】Modulation of membrane dynamics and cell motility by membrane tension
戴建武, Michael P. Sheetz and Jianwu Dai
trends in CELL BIOLOGY (Vol. 6) March 1996,-0001,():
-1年11月30日
The plasma membrane of most cells is drawn tightly over the cytoskeleton of the cell, resulting in a significant tension being developed in the membrane. The tension in the membrane can be calculated fi-om the force required to separate it ffom the cytoskeleton; and the force itself can be measured rapidly by using laser tweezers. Recent observations indicate that decreasing membrane tension stimulates endocytosis and increasing tension stimulates secretion. Thus, membrane tension provides a simple physical mechanism to control the area of the plasma membrane. Here, we speculate that tension is a global parameter that the cell uses to control physically plasma membrane dynamics, cell shape and cell motility.
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【期刊论文】Axon Membrane Flows from the Growth Cone to the Cell Body
戴建武, Jianwu Dai and Michael P. Sheetz
Cell, Vol. 63, 693-701, December 1, 1995, Copyright,-0001,():
-1年11月30日
During the growth of axons, the surface area of the neuron increases dramatically. Membrane addition as well as exchange could contribute to rapid membrane dynamics or flow. Using diffusing latex beads to monitor membrane flow, we find that axonal membrane flows rapidly (7 pm/mm) from growth cone to cell body during axon growth and that flow is inhibited by brefeldin A. To power this flow, there is a membrane tension gradient from growth cone to cell body that could draw the membrane overtheaxon at that rate. Further, when an artificial flow is induced to the center of the axon by use of laser tweezers, the primary source of the membrane is from the growth cone. We suggest that during neuron growth, there is excess membrane added at the growth cone in chick dorsal root ganglia (DRGs) that undergoes endocytosis at the cell body, thereby creating a flow that can rapidly alter the content of the axon membrane.
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戴建武, Jianwu Dai and Michael P. Sheetz
Biophysical Journal Volume 68 March 1995 988-996,-0001,():
-1年11月30日
Many cell phenomena involve major morphological changes, particularly in mitosis and the process of cell migration. For cells or neuronal growth cones to migrate, they must extend the leading edge of the plasma membrane as a lamellipodium or filopodium. During extension of filopodia, membrane must move across the surface creating shear and flow. Intracellular biochemical processes driving extension must work against the membrane mechanical properties, but the forces required to extend growth cones have not been measured. In this paper, laser optical tweezers and a nanometer-level analysis system were used to measure the neuronal growth cone membrane mechanical properties through the extension of filopodia-like tethers with IgG-coated beads. Although the probability of a bead attaching to the membrane was constant irrespective of treatment; the probability of forming a tether with a constant force increased dramatically with cytochalasin B or D and dimethylsulfoxide (DMSO). These are treatments that alter the organization of the actin cytoskeleton. The force required to hold a tether at zero velocity (F0) was greater than forces generated by single molecular motors, kinesin and myosin; and F0 decreased with cytochalasin B or D and DMSO in correlation with the changes in the probability of tether formation. The force of the tether on the bead increased linearly with the velocity of tether elongation. From the dependency of tether force on velocity of tether formation, we calculated a parameter related to membrane viscosity, which decreased with cytochalasin B or D, ATP depletion, nocodazole, and DMSO. These results indicate that the actin cytoskeleton affects the membrane mechanical properties, including the force required for membrane extension and the viscoelastic behavior.
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【期刊论文】Integrin-Cytoskeletal Interactions in Neuronal Growth Cones
戴建武, Christine E. Schmidt, Jianwu Dai, Douglas A. Lauffenburger, l, Michael P. Sheetz, and Alan F. Horwitz
The Journal of Neuroscience, May 1995, 15 (5): 3400-3407,-0001,():
-1年11月30日
Development of the nervous system requires that neuronal growth cones, in coordination with growing axons, migrate along precise paths defined by specific extracellular matrix cues until they ncounter their targets. Laminin promotes growth cone migration through receptors such as the integrins, but the underlying physical mechanism is poorly understood. We have investigated the cytoskeletal associations and surface dynamics of endogenous β1 integrins in chick dorsal root ganglion growth cones migrating on laminin. A single-beam optical gradient trap was used to place 0.5-µm-diameter polystyrene beads conjugated with anti-β1 integrin monoclonal antibodies at desired locations on the growth cone surface. We found a substantial increase in the stable attachment of these beads, with subsequent slow rearward motion, on the front periphery of the growth cone compared to the ase. The surface dynamics of smaller aggregates of integrin were explored by monitoring the temporal and spatial displacements of 40-nm-diameter gold particles coated with anti-β1 integrin antibodies. The small particles were transported preferen tially to the growth cone periphery by brief directed xcursions interspersed with periods of diffusion. In addition, the leading edge of the growth cone was supported to a greater extent by an actin-dependent cytoskeleton that resisted mechanical tether formation. Such a regional differentiation of the growth cone has not been documented previously and has implications for the mechanism of growth cone migration and guidance.
nerve growth cone,, migration,, motility,, integrin,, cytoskeleton,, laser optical trap,, single-particle tracking
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