Abstract:
:Autocrine loops formed by growth factors and their receptors have been identified in a large number of developmental, physiological, and pathological contexts. In general, the spatially distributed and recursive nature of autocrine signaling systems makes their experimental analysis, and often even their detection, very difficult. Here, we combine Brownian motion theory, Monte Carlo simulations, and reaction-diffusion models to analyze the spatial operation of autocrine loops. Within this modeling framework, the ability of autocrine cells to recapture the endogenous ligand and the distances traveled by autocrine ligands are explicitly related to ligand diffusion coefficients, density of surface receptors, ligand secretion rate, and rate constants of ligand binding and endocytic internalization. Applying our models to study autocrine loops in the epidermal growth factor receptor system, we find that autocrine loops can be highly localized--even at the level of a single cell. We demonstrate how the variations in molecular and cellular parameters may "tune" the spatial range of autocrine signals over several orders of magnitude: from microns to millimeters. We argue that this versatile regulation of the spatial range of autocrine signaling enables autocrine cells to perceive a broad spectrum of environmental information.
journal_name
Biophys Jjournal_title
Biophysical journalauthors
Shvartsman SY,Wiley HS,Deen WM,Lauffenburger DAdoi
10.1016/S0006-3495(01)75837-7subject
Has Abstractpub_date
2001-10-01 00:00:00pages
1854-67issue
4eissn
0006-3495issn
1542-0086pii
S0006-3495(01)75837-7journal_volume
81pub_type
杂志文章abstract::TOK1 encodes the channel responsible for the prominent outward K(+) current of the yeast plasma membrane. It can dwell in several impermeable states, including a rapidly transiting, K(+)-electromotive-force-dependent "R" (rectifying) state, a voltage-independent "IB" (interburst) state, and a set of [K(+)](ext) and vo...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(02)75440-4
更新日期:2002-02-01 00:00:00
abstract::Cellular plasma membranes have domains that are defined, in most cases, by cytoskeletal elements. The outer half of the bilayer may also contain domains that organize glycosylphosphatidylinositol (GPI)-linked proteins. To define outer membrane barriers, we measured the resistive force on membrane bound beads as they w...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(00)76306-5
更新日期:2000-07-01 00:00:00
abstract::Recent suggestions of nanoscale heat confinement on the surface of synthetic and biogenic magnetic nanoparticles during heating by radio frequency-alternating magnetic fields have generated intense interest because of the potential utility of this phenomenon for noninvasive control of biomolecular and cellular functio...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2020.01.028
更新日期:2020-03-24 00:00:00
abstract::Pore formation by membrane-active peptides, naturally encountered in innate immunity and infection, could have important medical and technological applications. Recently, the well-studied lytic peptide melittin has formed the basis for the development of combinatorial libraries from which potent pore-forming peptides ...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2020.02.024
更新日期:2020-04-21 00:00:00
abstract::Multiple nanosecond duration molecular dynamics simulations were performed on the transmembrane region of the Torpedo nicotinic acetylcholine receptor embedded within a bilayer mimetic octane slab. The M2 helices and M2-M3 loop regions were free to move, whereas the outer (M1, M3, M4) helix bundle was backbone restrai...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1529/biophysj.104.052878
更新日期:2005-05-01 00:00:00
abstract::A ternary lipid mixture of palmitoyl-oleoyl-phosphatidylcholine (POPC), palmitoyl-erythro-sphingosylphosphorylcholine (PSM), and cholesterol at a mixing ratio of 37.5:37.5:25 mol/mol/mol was characterized using fluorescence microscopy, (2)H NMR, and electron paramagnetic resonance spectroscopy. The synthetic PSM provi...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1529/biophysj.107.112904
更新日期:2008-04-01 00:00:00
abstract::The change in capacity of squid axon membrane during hyper- and depolarizations was investigated in the absence of ionic currents after the membrane was treated with pronase. In the presence of the inactivation process (h parameter), failure to observe the gating current in the frequency domain was attributed to the r...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(78)85475-7
更新日期:1978-04-01 00:00:00
abstract::ATP, 2-deoxy ATP (dATP), CTP, and UTP support isometric force and unloaded shortening velocity (Vu) to various extents (Regnier et al., Biophys. J. 74:3044-3058). Vu correlated with the rate of cross-bridge dissociation after the power stroke and the steady-state hydrolysis rate in solution, whereas force was modulate...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(98)78013-0
更新日期:1998-06-01 00:00:00
abstract::Hyaluronan (HA) is a highly hydrated polyanion, which is a network-forming and space-filling component in the extracellular matrix of animal tissues. Confocal fluorescence recovery after photobleaching (confocal-FRAP) was used to investigate intramolecular hydrogen bonding and electrostatic interactions in hyaluronan ...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(99)77061-X
更新日期:1999-10-01 00:00:00
abstract::The viral genome and replicative enzymes of the human immunodeficiency virus are encased in a shell consisting of assembled mature capsid protein (CA). The core shell is a stable, effective protective barrier, but is also poised for dissolution on cue to allow transmission of the viral genome into its new host. In thi...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(01)75725-6
更新日期:2001-07-01 00:00:00
abstract::The dependence of phospholipid vesicle size on lipid composition is investigated by photon correlation spectroscopy. For each lipid composition prolonged ultracentrifugation was used to isolate a nearly uniform population of minimum-sized vesicles. The residual size variations in the samples were sufficient to cause p...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(82)84524-4
更新日期:1982-04-01 00:00:00
abstract::Solute transport through the extracellular matrix is essential for cellular activities in articular cartilage. Increased solute transport via fluid convection may be a mechanism by which dynamic compression stimulates chondrocyte metabolism. However, loading conditions that optimally augment transport likely vary for ...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1529/biophysj.105.080366
更新日期:2006-08-15 00:00:00
abstract::Membrane proteins diffuse within the membrane, form oligomers and supramolecular assemblies. Using high-speed atomic force microscopy, we present direct experimental measure of an in-membrane-plane interaction potential between membrane proteins. In purple membranes, ATP-synthase c-rings formed dimers that temporarily...
journal_title:Biophysical journal
pub_type: 信件
doi:10.1016/j.bpj.2010.07.028
更新日期:2010-10-06 00:00:00
abstract::A theory of molecular motors is presented that explains how the energy released in single chemical reactions can generate mechanical motion and force. In the simplest case the fluctuating movements of a motor enzyme are well described by a diffusion process on a two-dimensional potential energy surface, where one dime...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(00)76615-X
更新日期:2000-02-01 00:00:00
abstract::A partially depolarized squid axon membrane is assumed to have a quasi-steady state negative resistance, the membrane potential is clamped at one point, and a distribution of potential along the axon is obtained from the cable equation. Nominal experimental values of -2 ohm cm(2) for the membrane and 6 ohm cm(2) for t...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/s0006-3495(61)86898-7
更新日期:1961-05-01 00:00:00
abstract::Calmodulin (CaM) is a highly flexible calcium-binding protein that mediates signal transduction through an ability to differentially bind to highly variable binding sequences in target proteins. To identify how binding affects CaM motions, and its relationship to conformational entropy and target peptide sequence, we ...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2012.08.037
更新日期:2012-10-03 00:00:00
abstract::The arrangement of side chains in alpha-helical regions of protein can be represented by helical net-diagrams. The addition of quantitative indices of the character of the residue at each net-point facilitates a straightforward examination of the groupings of residues of different character. As such the method complem...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(68)86525-7
更新日期:1968-07-01 00:00:00
abstract::Root mean-square deviation (RMSD) after roto-translational least-squares fitting is a measure of global structural similarity of macromolecules used commonly. On the other hand, experimental x-ray B-factors are used frequently to study local structural heterogeneity and dynamics in macromolecules by providing direct i...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2009.11.011
更新日期:2010-03-03 00:00:00
abstract::Using both analytical solutions obtained from simplified systems and numerical results from more realistic cases, we investigate the role played by the dielectric constant of membrane proteins epsilon(p) and pore water epsilon(w) in permeation of ions across channels. We show that the boundary and its curvature are th...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(03)70015-0
更新日期:2003-05-01 00:00:00
abstract::The plasma membrane (PM) serves as the functional interface between a cell and its environment, hosting extracellular signal transduction and nutrient transport among a variety of other processes. To support this extensive functionality, PMs are organized into lateral domains, including ordered, lipid-driven assemblie...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2016.03.012
更新日期:2016-04-26 00:00:00
abstract::We report evidence for an unconventional type of allosteric regulation of a biomotor. We show that the genome-packaging motor of phage ϕ29 is regulated by a sensor that detects the density and conformation of the DNA packaged inside the viral capsid, and slows the motor by a mechanism distinct from the effect of a dir...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2014.11.3469
更新日期:2015-01-20 00:00:00
abstract::The AXH domain of protein Ataxin 1 is thought to play a key role in the misfolding and aggregation pathway responsible for Spinocerebellar ataxia 1. For this reason, a molecular level understanding of AXH oligomerization pathway is crucial to elucidate the aggregation mechanism, which is thought to trigger the disease...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2017.11.025
更新日期:2018-01-23 00:00:00
abstract::On the basis of its role in the analysis of mammillary compartmental systems, a matrix with non-zero elements in the first row, first column, and along the main diagonal and with zero elements elsewhere is called a mammillary matrix. It is pointed out that such matrices occur in a variety of biological problems includ...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/s0006-3495(64)86769-2
更新日期:1964-01-01 00:00:00
abstract::Quantitative relationships between inputs and outputs of signaling systems are fundamental information for the understanding of the mechanism of signal transduction. Here we report the correlation between the number of epidermal growth factor (EGF) bindings and the response probability of intracellular calcium elevati...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1529/biophysj.104.053330
更新日期:2005-05-01 00:00:00
abstract::Viral infection begins with the binding of a virus to a specific target on the surface of the host cell, followed by viral genome delivery into the host and a continuation of the infection process. Before binding occurs, the virus must first find its receptor by a process whose details are largely unknown. We applied ...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2011.05.014
更新日期:2011-06-22 00:00:00
abstract::Sharing of positive or negative regulators between multiple targets is frequently observed in cellular signaling cascades. For instance, phosphatase sharing between multiple kinases is ubiquitous within the MAPK pathway. Here we investigate how such phosphatase sharing could shape robustness and evolvability of the ph...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2017.10.037
更新日期:2018-01-09 00:00:00
abstract::Multiple data are available on the self-assembly of mixtures of bilayer-forming amphiphiles, particularly phospholipids and micelle-forming amphiphiles, commonly denoted detergents. The structure of such mixed assemblies has been thoroughly investigated, described in phase diagrams, and theoretically rationalized in t...
journal_title:Biophysical journal
pub_type: 杂志文章,评审
doi:10.1016/j.bpj.2013.06.007
更新日期:2013-07-16 00:00:00
abstract::Effects of adducts of [PtCl(NH3)3]Cl or chlorodiethylenetriamineplatinum(II) on DNA stability were studied with emphasis on thermodynamic origins of that stability. Oligodeoxyribonucleotide duplexes (15-bp) containing the single, site-specific monofunctional adduct at G-residues of the central sequences TGT/ACA or 5'-...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1529/biophysj.104.051771
更新日期:2005-02-01 00:00:00
abstract::Lipid droplets (LDs) are cytosolic organelles that protrude from the endoplasmic reticulum membrane under energy-rich conditions. How an LD buds off from the endoplasmic reticulum bilayer is still elusive. By using a continuous media description, we computed the morphology of a lipid droplet embedded in between two id...
journal_title:Biophysical journal
pub_type: 信件
doi:10.1016/j.bpj.2017.05.045
更新日期:2017-07-11 00:00:00
abstract::A subsarcolemmal tubular system network (SSTN) has been detected in skeletal muscle fibers by confocal imaging after the removal of the sarcolemma. Here we confirm the existence and resolve the fine architecture and the localization of the SSTN at an unprecedented level of detail by examining extracellularly applied t...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2013.04.029
更新日期:2013-06-04 00:00:00