Colloidal gels from proteins and peptides - Physical Gels from Biological and Synthetic Polymers - page 277

reassembly of proteins produces architectures that exhibit the same molecular and
supramolecular structures as their in vivo counterparts, indicating that self-assembly is
driven by thermodynamic equilibrium determined by external conditions such as ionic
strength, temperature and pH. Self-assembly kinetics is typically very slow or very fast
depending on the growth phase, making it dif cult to observe the processes in equili-

brium conditions. The in vitro formation of such

fibres results from a very slow
nucleation stage followed by a very fast growth stage. These inherent dif

culties are
further complicated by the existence of simultaneous pathways leading to various
morphologies that have been experimentally observed or predicted by molecular
dynamics.
The application of model , both as ways of understanding disease states and

as interesting modern materials, is a very active area. Useful recent reviews and articles
include Chiti and Dobson ( 2006 ) and Pedersen and Otzen ( 2008 ). Their suggested use as
nanomaterials is discussed by Cherny and Gazit ( 2008 ).

' amyloids '

9.5 Specific assemblies from peptides and proteins

There are many examples of fibril formation involving more speci c assembly mecha-

nisms, including the formation of actin and tubulin fibrils, which play a role in the

properties of the cytoskeleton or fibrin gel in blood clots (Shah and Janmey, 1997 ;

Janmey et al., 1998 ). Fibrinogen may also be considered to fall into this category.
Although its assembly into fibrin (the mechanism of blood clotting) requires chemical

cross-linking ( ' ligation ' ), there is work on unligated fibrin gels, and we discuss this

brie y below. Although all of these systems are critical to in vivo function, we restrict

ourselves to in vitro work on pure components and/or very simple mixtures.

9.5.1 Insulin and lysozyme gels

Insulin is the pancreatic hormone involved in glucose transport, and the failure of this
mechanism gives rise to the various forms of diabetes. Insulin is a small globular protein,
but for many years it has been known that, when heated above its unfolding temperature,
particularly at acid pH, an opalescent gel can be formed, with critical concentration
around 1%. Electron microscope studies have showed that the gel consists of long, large
persistence length fibrils, with minimum strand thicknesses around 5 - 10 nm (Clark et al.,

1981a ). More recent studies have con bril

thickness are lower by a factor 2 (Gosal et al., 2004b ). Secondary structure measurements
have shown an increase in

rmed this using AFM, although estimates for

β -sheet, and an early paper established this to be of parallel

β

cross- fibrils seems to follow the spherulitic pattern reported by

Donald and co-workers for other amyloid protein gels (Domike and Donald, 2009 );
consequently it can be regarded as the prototype of these. Images tend to suggest that the
'

structure. Growth of the

gel appearance reported
would suggest that they are somewhat different from the other heat-set gels discussed in
this chapter, and more akin to the hydrophobic gels discussed in Chapter 6 .

gel ' structure is made up of intertwined fibrils, and the ' pasty '