Lateral diffusion of PDGF β-receptors in human fibroblasts

Ljungquist-Höddelius, Pia; Lirvall, Margareta; Wasteson, Åke; Magnusson, Karl‐Eric

doi:10.1007/bf01118604

Cited by 14 publications

(9 citation statements)

References 37 publications

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“…4). Although the results were calculated from a small number of samples, they are consistent with earlier work on the effect of serum on PDGF-ß receptor mobilities [16,17]. As has been noted, addition of serum increased the diffusion coefficient and mobile fraction of PDGF-ß receptors as detected in these FRAP studies.…”

Section: Discussionsupporting

confidence: 89%

“…To elucidate basal mobility characteristics of the PDGF receptor in the fibroblast membrane, and to investigate the effects of serum and PDGF stimulation, experiments were conducted [16,17] utilizing the previously described technique of fluorescence recovery after photobleaching (FRAP) [18][19][20]. Using this method, it is possible to measure the rate of lateral diffusion and estimate the fraction of mobile PDGF receptors in human fibroblasts.…”

Section: Introductionmentioning

confidence: 99%

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Aggregation of PDGF‐β receptors in human skin fibroblasts: characterization by image correlation spectroscopy (ICS)

et al. 1997

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Receptor aggregation is believed to be an important, early step when growth factors such as PDGF stimulate proliferation and differentiation of cell populations. To investigate receptor aggregation, we utilized a novel biophysical technique, image correlation spectroscopy, to study the distribution and aggregation state of PDGF-ß receptors on the surface of human dermal fibroblasts under various experimental conditions. It was found that the cell surface receptors were pre-clustered at 4°C and receptor aggregation increased for samples measured at 37°C. Treatment with PDGF-BB had no measurable effect on the receptor aggregation state. The results also indícate that additions of 10% serum or an inhibitor of tyrosine kinase activity, may disperse the receptors. The results of this study are consistent with organization of PDGF-ß receptors in pre-existing membrane domains.

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Aggregation of PDGF‐β receptors in human skin fibroblasts: characterization by image correlation spectroscopy (ICS)

et al. 1997

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“…The speed of diffusion of receptors can vary depending on receptor and cell type. However, well-known receptors in chemotaxis such as EGFR in human mammary epithelial cells, TrkA in growth cones and PDGF in fibroblasts have diffusion constants of the order of 10 21 to 10 22 mm 2 s 21 [25,29,16]. In the typical time it takes cells to respond to chemical gradients, i.e.…”

Section: Discussionmentioning

confidence: 99%

How receptor diffusion influences gradient sensing

Nguyen

Dayan

Goodhill

2015

J. R. Soc. Interface.

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Chemotaxis, or directed motion in chemical gradients, is critical for various biological processes. Many eukaryotic cells perform spatial sensing, i.e. they detect gradients by comparing spatial differences in binding occupancy of chemosensory receptors across their membrane. In many theoretical models of spatial sensing, it is assumed, for the sake of simplicity, that the receptors concerned do not move. However, in reality, receptors undergo diverse modes of diffusion, and can traverse considerable distances in the time it takes such cells to turn in an external gradient. This sets a physical limit on the accuracy of spatial sensing, which we explore using a model in which receptors diffuse freely over the membrane. We find that the Fisher information carried in binding and unbinding events decreases monotonically with the diffusion constant of the receptors.

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“…However, well-known receptors in chemotaxis such as EGFR in human mammary epithelial cells, TrkA in growth cones and PDGF in fibroblasts have diffusion constants of the order of 10 −10 cm 2 /s [213,221,227]. In the typical time that it takes cells to respond to chemical gradients, i.e., around a few minutes, the mean square displacement of receptors can be comparable to cell size (several micrometers).…”

Section: Discussionmentioning

confidence: 99%

“…Diffusion constants of relevant receptors such as epidermal growth factor receptor (EGFR) and platelet derived factor receptors (PDFR) are of order 10 −2 µm 2 /s while the dissociation constants are of order 10 −1 s, suggesting that this approximation is valid at K d and higher concentrations [220][221][222][223][224].…”

Section: Mobile Receptorsmentioning

confidence: 99%

Mathematical modelling of axon guidance in chemical gradients

Nguyen¹

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Correct wiring is crucial to the proper functioning of the nervous system. Key signals guiding growth cones, the motile tips of developing axons, to their targets are molecular gradients. The receptors on the membrane of the growth cone bind stochastically with guidance molecules in the environment, giving an estimate of the direction of the gradient. The growth cone then executes biased random movements to navigate toward the chemoattractant source or away from the chemorepellent source. This thesis addresses two questions: 1) how the positioning and diffusion of receptors on the growth cone membrane affect the accuracy of gradient estimation, 2) how trajectories are influenced by chemical gradients.Membrane receptors can diffuse freely on the membrane, smearing out the directional information about the gradient. It was unknown how the positioning and diffusion of receptors affect the estimate of the gradient. To address question (1) above, we utilise an ideal-observer approach, assuming that the growth cone can perform maximum likelihood estimation of the gradient based on the stochastic binding patterns with ligand molecules. The performance of gradient sensing is measured by the Fisher Information between the binding pattern and the gradient direction. The quality of gradient sensing decreases with higher diffusion constant of the receptors and improves with higher concentration. We then extend to a two-dimensional model of an elliptical growth cone with a general prior distribution. With a random uniform distribution of receptors, the shape of the growth cone can introduce bias in the gradient estimate. This bias can be corrected by a non-uniform distribution of receptors with higher density near the minor axis of the growth cone.Besides stochastic gradient sensing, growth cones also trace highly stochastic trajectories, and it is unclear how molecular gradients bias their movement. We then introduce a mathematical model of a correlated random walk based on persistence, bias and noise to describe growth cone trajectories, constrained directly by measurements of the detailed statistics of growth cone movements in both attractive and repulsive gradients in a microfluidic device. This model explains the long-standing mystery that average axon turning angles in gradients in vitro plateau very rapidly with time at relatively small values of 10-20• . This work introduces the most accurate predictive model of growth cone trajectories to date, and calls into question the ability of molecular gradients alone to provide reliable guidance cues for growing axons.ii Declaration by AuthorThis thesis is composed of my original work, and contains no material previously published or written by another person except where due reference has been made in the text. I have clearly stated the contribution by others to jointly-authored works that I have included in my thesis.

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Lateral diffusion of PDGF β-receptors in human fibroblasts

Cited by 14 publications

References 37 publications

Aggregation of PDGF‐β receptors in human skin fibroblasts: characterization by image correlation spectroscopy (ICS)

Aggregation of PDGF‐β receptors in human skin fibroblasts: characterization by image correlation spectroscopy (ICS)

How receptor diffusion influences gradient sensing

Mathematical modelling of axon guidance in chemical gradients

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