Fiber depolymerization: fracture, fragments, vanishing times, and stochastics in sickle hemoglobin

Jiang Cheng Wang, Suzanna Kwong, Frank A. Ferrone, Matthew S. Turner, Robin W. Briehl

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The well-characterized rates, mechanisms, and stochastics of nucleation-dependent polymerization of deoxyhe- moglobin S (HbS) are important in governing whether or not vaso-occlusive sickle cell crises will occur. The less well studied kinetics of depolymerization may also be important, for example in achieving full dissolution of polymers in the lungs, in resolution of crises and/or in minimizing gelation-induced cellular damage. We examine depolymerization by microscopic observations on depolymerizing HbS fibers, by Monte Carlo simulations and by analytical characterization of the mechanisms. We show that fibers fracture. Experimental scatter of rates is consistent with stochastic features of the analytical model and Monte Carlo results. We derive a model for the distribution of vanishing times and also show the distribution of fracture-dependent fiber fragment lengths and its time dependence. We describe differences between depolymerization of single fibers and bundles and propose models for bundle dissolution. Our basic model can be extended to dissolution of gels containing many fibers and is also applicable to other reversible linear polymers that dissolve by random fracture and end-depolymerization. Under the model, conditions in which residual HbS polymers exist and facilitate repolymerization and thus pathology can be defined; whereas for normal polymers requiring cyclic polymerization and depolymerization for function, conditions for rapid cycling due to residual aggregates can be identified.

Original languageEnglish (US)
Pages (from-to)655-670
Number of pages16
JournalBiophysical Journal
Volume96
Issue number2
DOIs
StatePublished - Jan 21 2009

Fingerprint

Sickle Hemoglobin
Polymers
Polymerization
Gels
Pathology
Lung

ASJC Scopus subject areas

  • Biophysics

Cite this

Fiber depolymerization : fracture, fragments, vanishing times, and stochastics in sickle hemoglobin. / Wang, Jiang Cheng; Kwong, Suzanna; Ferrone, Frank A.; Turner, Matthew S.; Briehl, Robin W.

In: Biophysical Journal, Vol. 96, No. 2, 21.01.2009, p. 655-670.

Research output: Contribution to journalArticle

Wang, Jiang Cheng ; Kwong, Suzanna ; Ferrone, Frank A. ; Turner, Matthew S. ; Briehl, Robin W. / Fiber depolymerization : fracture, fragments, vanishing times, and stochastics in sickle hemoglobin. In: Biophysical Journal. 2009 ; Vol. 96, No. 2. pp. 655-670.
@article{6159ef9da52b4fe2ad7a4b221b90c5df,
title = "Fiber depolymerization: fracture, fragments, vanishing times, and stochastics in sickle hemoglobin",
abstract = "The well-characterized rates, mechanisms, and stochastics of nucleation-dependent polymerization of deoxyhe- moglobin S (HbS) are important in governing whether or not vaso-occlusive sickle cell crises will occur. The less well studied kinetics of depolymerization may also be important, for example in achieving full dissolution of polymers in the lungs, in resolution of crises and/or in minimizing gelation-induced cellular damage. We examine depolymerization by microscopic observations on depolymerizing HbS fibers, by Monte Carlo simulations and by analytical characterization of the mechanisms. We show that fibers fracture. Experimental scatter of rates is consistent with stochastic features of the analytical model and Monte Carlo results. We derive a model for the distribution of vanishing times and also show the distribution of fracture-dependent fiber fragment lengths and its time dependence. We describe differences between depolymerization of single fibers and bundles and propose models for bundle dissolution. Our basic model can be extended to dissolution of gels containing many fibers and is also applicable to other reversible linear polymers that dissolve by random fracture and end-depolymerization. Under the model, conditions in which residual HbS polymers exist and facilitate repolymerization and thus pathology can be defined; whereas for normal polymers requiring cyclic polymerization and depolymerization for function, conditions for rapid cycling due to residual aggregates can be identified.",
author = "Wang, {Jiang Cheng} and Suzanna Kwong and Ferrone, {Frank A.} and Turner, {Matthew S.} and Briehl, {Robin W.}",
year = "2009",
month = "1",
day = "21",
doi = "10.1016/j.bpj.2008.04.001",
language = "English (US)",
volume = "96",
pages = "655--670",
journal = "Biophysical Journal",
issn = "0006-3495",
publisher = "Biophysical Society",
number = "2",

}

TY - JOUR

T1 - Fiber depolymerization

T2 - fracture, fragments, vanishing times, and stochastics in sickle hemoglobin

AU - Wang, Jiang Cheng

AU - Kwong, Suzanna

AU - Ferrone, Frank A.

AU - Turner, Matthew S.

AU - Briehl, Robin W.

PY - 2009/1/21

Y1 - 2009/1/21

N2 - The well-characterized rates, mechanisms, and stochastics of nucleation-dependent polymerization of deoxyhe- moglobin S (HbS) are important in governing whether or not vaso-occlusive sickle cell crises will occur. The less well studied kinetics of depolymerization may also be important, for example in achieving full dissolution of polymers in the lungs, in resolution of crises and/or in minimizing gelation-induced cellular damage. We examine depolymerization by microscopic observations on depolymerizing HbS fibers, by Monte Carlo simulations and by analytical characterization of the mechanisms. We show that fibers fracture. Experimental scatter of rates is consistent with stochastic features of the analytical model and Monte Carlo results. We derive a model for the distribution of vanishing times and also show the distribution of fracture-dependent fiber fragment lengths and its time dependence. We describe differences between depolymerization of single fibers and bundles and propose models for bundle dissolution. Our basic model can be extended to dissolution of gels containing many fibers and is also applicable to other reversible linear polymers that dissolve by random fracture and end-depolymerization. Under the model, conditions in which residual HbS polymers exist and facilitate repolymerization and thus pathology can be defined; whereas for normal polymers requiring cyclic polymerization and depolymerization for function, conditions for rapid cycling due to residual aggregates can be identified.

AB - The well-characterized rates, mechanisms, and stochastics of nucleation-dependent polymerization of deoxyhe- moglobin S (HbS) are important in governing whether or not vaso-occlusive sickle cell crises will occur. The less well studied kinetics of depolymerization may also be important, for example in achieving full dissolution of polymers in the lungs, in resolution of crises and/or in minimizing gelation-induced cellular damage. We examine depolymerization by microscopic observations on depolymerizing HbS fibers, by Monte Carlo simulations and by analytical characterization of the mechanisms. We show that fibers fracture. Experimental scatter of rates is consistent with stochastic features of the analytical model and Monte Carlo results. We derive a model for the distribution of vanishing times and also show the distribution of fracture-dependent fiber fragment lengths and its time dependence. We describe differences between depolymerization of single fibers and bundles and propose models for bundle dissolution. Our basic model can be extended to dissolution of gels containing many fibers and is also applicable to other reversible linear polymers that dissolve by random fracture and end-depolymerization. Under the model, conditions in which residual HbS polymers exist and facilitate repolymerization and thus pathology can be defined; whereas for normal polymers requiring cyclic polymerization and depolymerization for function, conditions for rapid cycling due to residual aggregates can be identified.

UR - http://www.scopus.com/inward/record.url?scp=58849106338&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=58849106338&partnerID=8YFLogxK

U2 - 10.1016/j.bpj.2008.04.001

DO - 10.1016/j.bpj.2008.04.001

M3 - Article

C2 - 19167311

AN - SCOPUS:58849106338

VL - 96

SP - 655

EP - 670

JO - Biophysical Journal

JF - Biophysical Journal

SN - 0006-3495

IS - 2

ER -