Subscriber access provided by University of Sussex Library
Article
Structural characterization of sodium alginate and calcium alginate Hadas Hecht, and Simcha Srebnik Biomacromolecules, Just Accepted Manuscript • DOI: 10.1021/acs.biomac.6b00378 • Publication Date (Web): 13 May 2016 Downloaded from http://pubs.acs.org on May 16, 2016
Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a free service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are accessible to all readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
Biomacromolecules is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.
Page 1 of 21
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
Biomacromolecules
Structural characterization of sodium alginate and calcium alginate Hadas Hecht † and Simcha Srebnik*‡ †
The Interdisciplinary Program in Polymer Engineering, Technion – Israel Institute of Technology, Haifa, Israel 32000 ‡
Department of Chemical Engineering, Technion – Israel Institute of Technology, Haifa, Israel 32000 Abstract Alginate readily aggregates and forms a physical gel in the presence of cations. The association of the chains, and ultimately gel structure and mechanics, depends not only on ion type, but also on the sequence and composition of the alginate chain that ultimately determines its stiffness. Chain flexibility is generally believed to decrease with guluronic residue content, but it is also known that both polymannuronate and polyguluronate chains are stiffer than heteropolymeric blocks. In this work, we use atomistic molecular dynamics simulation to primarily explore the association and aggregate structure of different alginate chains under various Ca2+ concentrations and for different alginate chain composition. We show that Ca2+ ions in general facilitate chain aggregation and gelation. However, aggregation is predominantly affected by alginate monomer composition, which is found to correlate with chain stiffness under certain solution conditions. In general, greater fractions of mannuronic monomers are found to increase chain flexibility of heteropolymer chains. Furthermore, differences in chain guluronic acid content are shown to lead to different interchain association mechanisms, such as lateral association, zipper mechanism and entanglement, where the mannuronic residues are shown to operate as elasticity moderator and therefore promote chain association.
* To whom correspondence should be addressed. E-mail:
[email protected].
ACS Paragon Plus Environment
1
Biomacromolecules
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
Page 2 of 21
Introduction Alginate is a polysaccharide that is quite abundant in nature and occurs both as a structural component in marine brown algae (phaeophyceae) and as capsular polysaccharide in soil bacteria. Industrial applications of alginates are found mainly in the food, medical, pharmaceutical and textile industries, and are linked to its ability to retain water, as well as its gelling, viscosifying, and stabilizing properties. Biotechnological applications are based on its instantaneous and almost temperature-independent physical crosslinking and its sol/gel transition in the presence of multivalent cations (e.g. Ca2+) in aqueous medium.1 The process is simple and cost effective resulting in physical gel with highly tunable mechanical properties.2 In addition, its capacity towards retaining large quantities of fluid make it highly suitable as immobilization matrix for various applications such as the delivery of drugs,3 genes or cells for tissue engineering and regenerative therapeutic applications,4 and sitespecific delivery to mucosal tissue due to alginates bioadhesivity.5 Alginates are linear copolymers composed of (1→4)-linked α-L-guluronic (G) and βD-mannuronic (M) residues of varying sequences depending on the organism and tissue that it is isolated from. The chains are composed of a random sequence of M- and G-blocks that are interspersed with regions of alternating MG blocks whose monad, diad and triad frequencies are known.6,7 Alginates in general are stiff molecules due to the rigid sixmembered sugar rings and restricted rotation around the glycosidic linkage. Electrostatic repulsion between the charged groups on the polymer chain further contributes to the rigidity of the chains. Chain stiffness is known to depend not only on ionic strength, but also on alginate composition, increasing in the order MGpoly-G/M.8 Our calculations shed light on the controversial dependence on Gcontent within heteropolymer chains, revealing that higher G content lead to stiffer chains at intermediate concentrations, with an unclear dependence on G content at low and high concentrations (Figure 5). Figure 5 suggests that the flexibility of individual chains may not correlate with G content, but at higher concentration when chain-chain interactions occurs, chain stiffness increases with G content for heteropolymers. This may be explained by the higher tendency towards aggregation of G blocks. This non-trivial dependence may also explain the variable conclusions found in the literature on the dependence of lp on alginate composition.8,14,38,42-44 Representative experimental values for the persistence length listed in Table 1 are quite similar for the various alginate compositions, where small differences in reported values have been attributed to measurement type, data processing method, and varying sample quality.45,46 The nontrivial dependence of alginate properties on polydispersity also complicates interpretation and comparison of results across experiments, that report on average properties only.32 Such variance experimental conditions does not explain the large discrepancy between our calculated persistence length and experimental measures for G-rich alginate. These high calculated values are attributed to the short (30-mer) chains considered in our study, whose contour length for poly-G is comparable to the calculated persistence
ACS Paragon Plus Environment
11
Biomacromolecules
length due to the compact egg-box conformation adopted by neighboring guluronic units, and hence places the G chains within the rigid rod regime. Indeed, the persistence length of low molecular weight polyguluronate has been measure to be as high as 50nm.47 We further analyze chain dimensions by measuring the contour length (𝐿! = !! !!!
𝑟!!! − 𝑟! ) and end-to-end distance (𝑅!! = 𝑟!! − 𝑟! ), and fitting these measures
to various polymer chain models (i.e., flexible, semiflexible, and rigid rod). 𝑟! in these definitions is the position vector of the ith monomer. As might be expected, the contour length of the chains varies little with concentration (results not shown) but decreases with G content (Figure 6a) since the guluronic residues prefer a more compact perpendicular orientation (Figure 1). However, the contour length does not grow linearly with increasing M content for the heteropolymer chains. Results shown in Figure 6 suggest that GGGG chains are generally shorter (lower L), stiffer (higher 𝑙! values) and straighter (𝑅!! ≈L) in comparison to other sequences, and particularly compared with the heteropolymer sequences. In accord with Figure 1, MMMM chains, are significantly longer. As opposed to poly-G and poly-M, the heteropolymer chains reveal a decline in chain dimensions at high concentrations, since association leads to entanglement and coiling, as seen in the snapshots of Figure 2.
1
16
0.9
15
0.8
14
Ree/Lc
Contour length, nm
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
Page 12 of 21
13
0.7 0.6 0.5
12
0.3
11
(a)
GGGG GMGM GGGM
0.4 GGGG
GGGM GMGM GMMM MMMM
G content
(b)
0
5
MMMM GMMM
10 15 No. of Chains
20
Figure 6. (a) Contour length (Lc) and (b) normalized end-to-end distance (Ree/Lc) of alginate chains (Nm=30) for different alginate concentrations in Na+ solution (corresponding to 2-16 g/L) and sequences.
ACS Paragon Plus Environment
12
Page 13 of 21
Comparison was made to polymer chain models in order to characterize the nature of the chain conformation, whether flexible (𝑙! /𝐿1), or semi-flexible (𝑙! / 𝐿~1). The scaling of 𝑅!! ! for ideal (or freely-jointed) chain, Kratky-Porod model for semiflexible worm-like chains,48 and rigid rod chains, is given in Eqs. 4-6, respectively:
𝑅!! !
𝑅!! !
!"#
%$𝑅!! !
!"#$!!"#$%&"#
!"#"$
=𝐿∗𝑙
= 2𝑙! 𝐿 1 −
(4) = 𝐿!
!! !
(5)
1−𝑒
!!
!!
(6)
Insertion of the measured values for contour length and calculated persistence length obtained from the simulations into these three models and comparison with the calculated mean squared end-to-end distance gives indication of the nature of the chain.
ΔdevR
60
Devia/on from model
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
Biomacromolecules
DdR
50 40
8 7 6 5 4 3 2 1 0
ideal
poly-M poly-G
semi-flexible rigid
0
5
10
15
20
No. of chains
30 20 10 0 0
0.33
0.5
G content
0.66
1
Figure 7. Deviation of end-to-end distance from polymer chain models for ideal, semi-flexible, and rigid rod chains, for alginate chains in Na+ ion solution. Insert shows difference in the deviation from rigid and semi-flexible models for poly-M and poly-G alginate chains.
The mean squared deviations, 𝛿! =
𝑅!!
!"#
− 𝑅!!
! !"#
%$, of the calculated
value from each model are shown in Figure 7. In general, all simulated alginates fit the semiflexible chain model most closely. However, the homopolymeric alginates, and poly-M in
ACS Paragon Plus Environment
13
Biomacromolecules
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
Page 14 of 21
particular, show a reasonable fit to the rigid rod scaling as well, with a clear transition towards rigid rod behavior at high concentrations, plotted as 𝛿!,!"#$% − 𝛿!,!"#$!!"#$%&"# in Figure 7 (insert). The good fit of poly-G to rigid rod scaling (suggested by their high 𝑙! /𝐿 ratio) at all concentrations gives further support to the preferred rigid zigzag (egg-box) conformation of G blocks. The heteropolymer chains, on the other hand, tend towards flexible behavior at intermediate concentrations and above.
Ca2+-alginate solution It is well known that alginates physically crosslink and gel in the presence of calcium ions at moderate conditions, which is the key to their technological applications. Gelation results from interactions between Ca2+ ions and the acidic sites on G residues in a cage-like (egg-box) configuration. The effect of alginate and Ca2+ on 𝑙! is shown in Fig. 8. The general trend
of
𝑙!
from
highest
to
lowest
follows
the
following
order
GGGG>MMMM>GGGM>GMGM>GMMM, similar to that found for Na+-alginate solutions at intermediate concentrations. Stokke et al.49 found the shear modulus to increase with alginate concentration, Ca2+ saturation, and G content. We find that while the homopolymer chains are strikingly stiffer than the heteropolymers, chain flexibility does appear to correlate with increasing G content for the heteropolymer chains in presence of Ca2+. However, we observe a generally decreasing trend of lp (which correlates with the elastic modulus50) with Ca2+ saturation, the origin of which is further discussed below. The propensity towards entanglement by the low G content GMMM chains at high alginate concentrations leads to an opposite trend for lp. GMMM also shows no dependence on Ca2+ concentration, giving further support to the caging of Ca2+ ions by adjacent G monomers.
ACS Paragon Plus Environment
14
Page 15 of 21
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
Biomacromolecules
100
GGGG MMMM GMGM GMMM GGGM
60 60 50 50 lp
lp 10
lp
40 40 30 30 20 20
GGGG GMGM GGGM
1 0
10 10
MMMM GMMM
5
0 0
0.01 10 No. of Chains
15
0.1
Ca2+ Satura1on
1
Figure 8. Persistence length of alginate in presence of of Ca2+ ions at various concentrations (a) averaged over Ca2+ concentrations and (b) averaged over alginate concentrations.
Similar to Na+-alginate solutions, alginate in the presence of Ca2+ acts predominantly as semi-flexible chains, with a tendency towards rigid chain for the homopolymers, and GGGG in particular. Figure 9 shows snapshots of the chains in the presence of Ca2+ ions at various concentrations. The semiflexible nature of the polymers has major implications for how they interact with each other to form entangled networks. Association is more predominant for the low G content chains, suggesting M monomers serve the role of flexibility moderators. Different associated conformations are observed, including dimerization, zipping, junction zones, coil and bundles, even at low Ca2+ ion concentrations. For GGGG chains, association occurs through sequential zippering between two or more chains as Ca2+ concentration increases Figure 9, A1-5), as more binding sites that allow for zipping of GG sequences are introduced. MMM chains, on the other hand, associate more readily at low ion concentrations, through fast dimerization. The stiffer and hence entropically more hindered GGGG chains (Figs. 6 and 7) are less likely to encounter one another due to random thermal fluctuations, as reviewed by Broedersz et al.51 Given the rigidity of semiflexible polymers at scales shorter than their contour length, they are fundamentally less prone to entangle with their neighbors since they cannot readily form tight coils or knots. This is easily envisioned in the extreme of a random static arrangement of
ACS Paragon Plus Environment
15
Biomacromolecules
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
Page 16 of 21
rigid rods, hence rigid polymers are inevitable less entangled than flexible polymers. In addition to the fundamental difference in stiffness of the chains, the distinct coordination geometries of the carboxylate and other oxygens in poly-G and poly-M chains give rise to higher local charged density of the latter, and hence greater long-range interaction resulting in enhanced association.22,23
A1
B1
C1
D1
E1
A2
B2
C2
D2
E2
A3
B3
C3
D3
E3
A4
B4
C4
D4
E4
Figure 9. Chains association in Ca2+-alginate solutions, for alginate concentration of Nc=5 (10gr/liter) and sequences with increasing G content (GGGG, GGGM, GMGM, GMMM, and MMMM for columns A through E, respectively) and different Ca2+ concentrations (corresponding to 0, 5-10 ,15-20 and ,25-30 mM) for rows 1 through 4, respectively.
More distinct configurations and difference between chain types are seen at high alginate concentration of Nc=15 (30gr/liter), shown in Figure 10. The stiff GGGG chains associate through linear bundles of trimers and tetramers and even larger bundles with increasing Ca2+ concentrations. Interestingly, MMMM chains show lateral association in
ACS Paragon Plus Environment
16
Page 17 of 21
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
Biomacromolecules
much broader junction zones. The more flexible heteropolymer chains show more disordered structures, with coiling and entanglement of the most flexible GMMM chains. Our results for GGGG chains agree with findings by Draget et al.,12 which have shown isolated and purified G-blocks to act as gelling modulators through the formation of junction zones made up of two or more chains (Fig. 9). Stewart et al.23 have shown poly-M decamers to aggregate in the presence of Ca2+ in a similar manner to poly-G decamers, via tight binding carboxylate bridging interactions, and suggested that poly-M regions may play a role in network assembly, as is noticeably seen in Figs. 8 and 9. Alternating MG sequences were suggested to play a role in the formation of mixed junctions between GG and MG blocks and even the formation of "secondary" junctions by "zipping" of long alternating MG sequences, which lead to partial network collapse at high calcium concentration,15,16 as seen for GMMM at high concentrations in our simulations.
A1
B1
C1
D1
E1
A2
B2
C2
D2
E2
A3
B3
C3
D3
E3
Figure 10. Chains association in Ca2+-alginate solutions, for alginate concentration of Nc=15 (30gr/liter) and sequences with increasing G content (GGGG, GGGM, GMGM, GMMM, and MMMM for columns A through E, respectively) and different Ca2+ concentrations (corresponding to 10 , 20 and , 30 mM) for rows 1 through 3, respectively.
ACS Paragon Plus Environment
17
Biomacromolecules
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
Page 18 of 21
Conclusions We presented detailed investigation of the effects of the G/M composition, alginate concentration and ion concentration on the structure and properties of alginate. A clear relation between chain stiffness and G content of alginate is observed at high alginate concentrations in Na+ solutions due to chain association. For Ca2+-alginate, chain stiffness appears to increase with G content essentially under all condition studied. Alginate chains were best fitted by the semi-flexible wormlike chain model, though the homopolymer GGGG and MMMM show a reasonable fit to rod-like chain models. The stiffer homopolymer chains association laterally, while the more flexible heteropolymer chains, and particularly the GMGM sequence, associate in coil-like configuration at high concentrations. Aggregate structures were shown to strongly depend on chain composition. In the presence of calcium ion, mannuronic acid residues operate as elasticity moderators and hence promote chains association. With increasing alginate concentrations, poly-M chains shift to lateral association of dimers and high order clusters, with no sign for zipper mechanism. Poly-G chain association initially occur through zipping, first of dimers followed by higher order clusters at more concentrated solutions. The heteropolymeric compositions reveal the formation of stiff zones connected by flexible junction, with more pronounced stiffness for sequence richer in G. Alginate association models ("egg-box" dimerization, zipper mechanism, lateral association, junction zones, bundles formation, flexible vs. stiff zones and coils formation) were clearly show to depend on the alginate G/M composition.
ACS Paragon Plus Environment
18
Page 19 of 21
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
Biomacromolecules
Bibliography (1)
(2) (3) (4) (5) (6) (7) (8) (9) (10) (11) (12) (13) (14) (15) (16) (17) (18) (19) (20) (21) (22) (23) (24) (25) (26) (27) (28) (29) (30)
Draget, K. I.; Smidsrød, O.; Skjåk-Bræk, G. In Polysaccharides and Polyamides in the Food Industry. Properties, Production and Patents; Vandamme, E. J., De Baets, S., Steinbüchel, A., Eds.; Wiley-VCH Verlag GmbH & Co. KGaA: Weinheim, Germany, 2005. Donati, I.; Mørch, Y. A.; Strand, B. L.; Skjåk-Bræk, G.; Paoletti, S. J. Phys. Chem. B 2009, 113 (39), 12916–12922. Josef, E.; Zilberman, M.; Bianco-Peled, H. Acta Biomater. 2010, 6 (12), 4642–4649. Smidsrød, O.; Skjåk-Bræk, G. Trends Biotechnol. 1990, 8, 71–78. Bitton, R.; Ben-Yehuda, M.; Davidovich, M.; Balazs, Y.; Potin, P.; Delage, L.; Colin, C.; Bianco-Peled, H. Macromol. Biosci. 2006, 6 (9), 737–746. Grasdalen, H.; Larsen, B.; Smidsrød, O. Carbohydr. Res. 1977. Stokke, B. T.; Smidsrød, O.; Bruheim, P.; Skjåk-Bræk, G. Macromolecules 1991, 24 (16), 4637–4645. Smidsrød, O.; Glover, R. M.; Whittington, S. G. Carbohydr. Res. 1973, 27 (1), 107– 118. Haug, A.; Smidsrød, O. Acta Chem. Scand. 1970, 24, 843–854. Grant, G. T.; Morris, E. R.; Rees, D. A.; Smith, P. J. C.; Thom, D. FEBS Lett. 1973, 32 (1), 195–198. Smidsrød, O.; Haug, A. Acta Chem. Scand. 1972, 26, 2063–2074. Draget, K. I.; Skjåk-Bræk, G.; Smidsrød, O. Int J Biol Macromol 1997, 21, 47–55. Hanwell, M. D.; Curtis, D. E.; Lonie, D. C.; Vandermeersch, T.; Zurek, E.; Hutchison, G. R. Journal of Cheminformatics. 2012, pp 1–17. Vold, I. M. N.; Kristiansen, K. A.; Christensen, B. E. Biomacromolecules 2006, 7, 2136–2146. Donati, I.; Holtan, S.; Mørch, Y. A.; Borgogna, M.; Dentini, M.; Skjåk-Bræk, G. Biomacromolecules 2005, 6, 1031–1040. Dentini, M.; Rinaldi, G.; Barbetta, A.; Risica, D. Carbohydr. Polym. 2007, 67, 465– 473. Braccini, I.; Grasso, R. P.; Perez, S. Carbohydr. Res. 1999, 317, 119–130. Braccini, I.; Pérez, S. Biomacromolecules 2001, 2, 1089–1096. Mackie, W.; Perez, S.; Rizzo, R.; Taravel, F.; Vignon, M. Int J Biol Macromol 1983, 5 (6), 329–341. Plazinski, W. Journal of Computational Chemistry 2011, 32 (14), 2988–2995. Plazinski, W.; Rudzinski, W. Struct Chem 2012, 23 (5), 1409–1415. Stewart, M. B.; Gray, S. R.; Vasiljevic, T.; Orbell, J. D. Carbohydr. Polym. 2014, 102, 246–253. Stewart, M. B.; Gray, S. R.; Vasiljevic, T.; Orbell, J. D. Carbohydr. Polym. 2014, 112, 486–493. Decho, A. W. Carbohydr. Res. 1999, 315, 330–333. Schmidt, R. K.; Tasaki, K.; Brady, J. W. J. Food Eng. 1994, 22 (1-4), 43–57. Edelman, R.; Kusner, I.; Kisiliak, R.; Srebnik, S.; Livney, Y. D. Food Hydrocolloids 2015, 48, 27–37. Kirschner, K. N.; Woods, R. J. Proc. Natl. Acad. Sci. U.S.A. 2001, 98 (19), 10541– 10545. Dashnau, J. L.; Sharp, K. A.; Vanderkooi, J. M. J. Phys. Chem. B 2005, 109 (50), 24152–24159. Plazinski, W. Carbohydr. Res. 2012, 357, 111–117. Sikorski, P.; Mo, F.; Skjåk-Bræk, G.; Stokke, B. T. Biomacromolecules 2007, 8 (7),
ACS Paragon Plus Environment
19
Biomacromolecules
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
(31) (32) (33) (34) (35) (36) (37) (38) (39) (40) (41) (42) (43) (44)
(45) (46) (47) (48) (49) (50) (51)
Page 20 of 21
2098–2103. Perić-Hassler, L.; Hunenberger, P. H. Mol. Simul. 2010, 36 (10), 778–795. Baños, F. G. D.; Peña, A. I. D.; Cifre, J. G. H.; Martínez, M. C. L.; Ortega, A.; la Torrea, de, J. G. Carbohydr. Polym. 2014, 102, 223–230. Plimpton, S.; Thompson, A.; Crozier, P. lammps.sandia.gov. Jorgensen, W. L.; Tirado-Rives, J. J. Am. Chem. Soc. 1988, 110 (6), 1657–1666. Wolnik, A.; Albertin, L.; Charlier, L.; Mazeau, K. Biopolymers 2013, 99 (8), 562– 571. Xiang, Y.; Liu, Y.; Mi, B.; Leng, Y. Langmuir 2013, 29 (37), 11600–11608. Xiang, Y.; Liu, Y.; Mi, B.; Leng, Y. Langmuir 2014, 30 (30), 9098–9106. Josef, E.; Bianco-Peled, H. Soft Matter 2012, 8 (35), 9156. Cerdà, J. J.; Sintes, T.; Chakrabarti, A. Macromolecules 2005, 38 (4), 1469–1477. Stokke, B. T.; Elgsaeter, A.; Skjrak-Brjek, G.; Smidsrød, O. Carbohydr. Res. 1987, 160, 13–28. Zhang, H.; Wang, H.; Wang, J.; Guo, R.; Zhang, Q. Polym. Adv. Technol. 2001, 12 (11‐12), 740–745. Whittington, S. G. Biopolymers 1971, 10 (9), 1481–1489. Mackie, W.; Noy, R.; Sellen, D. B. Biopolymers 1980, 19 (10), 1839–1860. Storz, H.; Müller, K. J.; Ehrhart, F.; Gómez, I.; Shirley, S. G.; Gessner, P.; Zimmermann, G.; Weyand, E.; Sukhorukov, V. L.; Forst, T.; Weber, M. M.; Zimmermann, H.; Kulicke, W.-M.; Zimmermann, U. Carbohydrate research. 2009, pp 985–995. Smidsrød, O. Carbohydrate research. 1970, pp 359–372. Martinsen, A.; Skjåk-Bræk, G.; Smidsrød, O. Carbohydrate Polymers. 1991, pp 171–193. Lee, K. Y.; Bouhadir, K. H.; Mooney, D. J. Biomacromolecules 2002, 3 (6), 1129– 1134. Hsu, H.-P.; Paul, W.; Binder, K. EPL 2010, 92 (2), 28003. Stokke, B. T.; Draget, K. I.; Smidsrød, O.; Yuguchi, Y.; Urakawa, H.; Kajiwara, K. Macromolecules 2000, 33 (5), 1853–1863. Haverkamp, R. G.; Williams, M. A. K.; Scott, J. E. Biomacromolecules 2005, 6 (3), 1816–1818. Broedersz, C. P.; MacKintosh, F. C. Rev. Mod. Phys. 2014, 86 (3), 995–1036.
ACS Paragon Plus Environment
20
Page 21 of 21
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
Biomacromolecules
Structural characterization of sodium alginate and calcium alginate Hadas Hecht and Simcha Srebnik
poly(GM)-Ca2+ alginate
poly(M)-Ca2+ alginate
Calcium alginate properties are strongly dependent on the relative fraction of guluronic (G) and mannuronic (M) residues. Homopolymers behave as semi-flexible polymers at high concentrations, while heteropolymers behave a flexible chains.
ACS Paragon Plus Environment
