hydrogel materials 
 are used in tissue engineering , microfluidics , and 
 drug delivery . a promising approach for the design of hydrogels 
 is the use of self - assembling 
 peptides in which noncovalent interactions between molecules drive 
 the assembly and formation of supramolecular fibril networks that 
 define the material . using peptides as building blocks , 
 one can form self - assembled structures that result in a percolated 
 hydrogel network . schneider and co - workers have designed a class of peptides that undergo triggered folding 
 into facially amphiphilic -hairpins that subsequently self - assemble 
 to form self - supporting , rigid hydrogels . recently , the kinetic and 
 mechanical rigidity of amphiphilic -hairpins were investigated 
 by chen et al . it forms two -strands consisting of alternating hydrophobic 
 valine and hydrophilic lysine residues connected by a tetrapeptide 
 sequence ( vppt ) designed to adopt a type 
 ii turn structure . in its folded state , hairpin amphiphilicity 
 is manifested in the composition of its faces : one hydrophobic valines , 
 the other hydrophilic lysine residues ( figure 1a ) . importantly , this amphiphilic folded state is highly prone to 
 self - assembly , forming a network of -sheet - rich fibrils . it 
 is known that temperature , ph , and ionic strength trigger the self - assembly 
 of max1 peptides . previously , it was shown that max1 self - assembles 
 under physiological conditions ( ph 7.4 and a temperature of 37 ) . small angle neutron scattering ( sans ) and transmission 
 electron microscopy ( tem ) studies demonstrated that the hairpin self - assembles 
 laterally , forming a network of intermolecular hydrogen bonds that 
 define the long axis of a given fibril . all the -strands of 
 the assembled hairpins are in register , affording fibrils with distinct 
 diameters of 3 nm . max1 facial self - assembly 
 can also take place by burial of the valine - rich face to form a bilayer 
 that defines the thickness of a given fibril . along the long axis 
 of a given fibril , bilayer formation occurs regularly with one hairpin 
 docked and in register with its partner , an arrangement that shields 
 the maximum surface area of the valine side chains from water ( figure 1b ) . it was suggested that imperfections in this 
 mechanism can occur where the face of one hairpin is rotated relative 
 to that of its bilayer partner , leading to nascent fibril growth in 
 three dimensions , forming an interfibril cross - link ( branch point ) . these branch points are noncovalent physical cross - links that define 
 the mechanical rigidity of the gel . although 
 light scattering and microscopy studies clarified the network and 
 the local fibril morphology , a detailed molecular - level model of how 
 the peptides arrange themselves within the fibrils remained elusive . herein , we constructed variant models of max1 peptide arrangements 
 and investigated the stability of each variant model . the first models the -hairpin arrangement 
 along the long axis of fibrils constituting the network . the second 
 models the -hairpin arrangement within the branch point regions 
 of the network . the third arrangement is an amyloid - like cross- 
 structure , i.e. , a -arch structure ( figure 1c and d ) . building blocks of the max1 hydrogel are composed of -hairpin 
 structures , not by an amyloid - like cross- arch . ( a ) a folded 
 -hairpin structure monomer of max1 peptide which presents intramolecular 
 hydrogen bonds . ( b ) two folded -hairpin structures of max1 
 peptide forming bilayer with a hydrophobic surface of valine residues . ( c ) a proposed model for a folded amyloid - like -arch monomer 
 of max1 peptide which does not present intramolecular hydrogen bonds . ( d ) two folded -arch structures of max1 peptide are assembled 
 into an amyloid - like cross- structure with intermolecular hydrogen 
 bonds . ( e ) a simulated self - assembled amyloid - like -arch structure 
 presents an unstable cross- structure . ( f and g ) a simulated 
 self - assembled -hairpin structure illustrates a structurally 
 stable fibrillar state . ( f ) a view along the fibril axis and ( g ) a 
 view from the side of the fibril . in parts a  c , valine and 
 lysine residues are colored as blue and red , respectively , and serine 
 residues are colored green . through extensive simulations , we found that the -hairpins 
 exhibit polymorphic packing along the fibril long axis and in the 
 branch points . previously , it was hypothesized that the cross - linking 
 phenomenon in max1 hydrogel is due to fibril imperfections . our simulations 
 show that -hairpin arrangements of branching structures are 
 preferred over -hairpin arrangements of long fibril structures . therefore , the hairpins are more favored to form branch points than 
 to pack along the long fibril axis . we thus conclude that short persistence 
 lengths of the self - assembled hairpins exist within the gel . in addition , 
 all possible arrangements illustrate that the type ii turns 
 that directly define the secondary structure of the -hairpins 
 do not form intermolecular interactions between the -hairpins 
 in the bilayer fibrils and thus do not contribute to the network morphology . md simulations of the solvated variant models 
 m1m8 and 
 other tested models were performed in the npt ensemble using the namd 
 program with the charmm27 force field for 60 ns . the models were explicitly solvated with tip3p water 
 molecules . the langevin piston method with a decay period of 100 fs 
 and a damping time of 50 fs the temperature ( 330 k ) was controlled by a langevin thermostat 
 with a damping coefficient of 10 ps . the short - range van der waals ( vdw ) interactions 
 were calculated using the switching function , with a twin range cutoff 
 of 10.0 and 12.0  . long - range electrostatic interactions were 
 calculated using the particle mesh ewald method with a cutoff of 12.0 
  for all simulations . the equations of motion 
 were integrated using the leapfrog integrator with a step of 2 fs . all initial variant models were energy minimized and then solvated 
 in a tip3p water box with a minimum distance of 15  from any 
 edge of the box to any -hairpin atom . the solvated systems were energy minimized for 2000 conjugated 
 gradient steps , where the distance between the -sheets in the 
 -hairpins is fixed in the range 2.22.5  . the minimized solvated systems were heated to 
 200 k , where all atoms were allowed to move . then , the systems were 
 heated from 200 to 250 k for 300 ps and equilibrated at 330 k for 
 300 ps . all simulations ran for 60 ns , and structures were saved every 
 10 ps for analysis . these conditions ( 330 k and 60 ns of time scales ) 
 are applied to test the stabilities of all variant models . we applied a higher temperature 
 than the physiological temperature ( 310 k ) , aiming to investigate 
 the stability of the variant models . the self - assembly of max1 peptides 
 is triggered by the higher temperature ; therefore , the choice of 330 
 k for md simulations is a reasonable choice . to obtain the relative 
 structural stability of the variant models , 
 the trajectories during the last 5 ns the solvation energies 
 of all systems were calculated using the generalized born method with 
 molecular volume ( gbmv ) . in the gbmv calculations , 
 the dielectric constant of water was set to 80.0 . the solvent - accessible 
 surface area ( sasa ) term factor was set to 0.00592 kcal / mol . each variant is minimized 1000 cycles , and the conformation 
 energy is evaluated by grid - based gbmv . the minimization does not 
 change the conformations of each variant but only relaxes the local 
 geometries due to thermal fluctuation which occur during the md simulations . a total of 4000 conformations ( 500 conformations for each of the 8 
 examined conformers ) were used to construct the free energy landscape 
 of the conformers and to evaluate the conformer probabilities by monte 
 carlo ( mc ) simulations . we based our constructed models on the overall 
 structure that had been proposed previously by schneider and co - workers : 
 the max1 peptide is composed of two -strands of alternating 
 lysine and valine residues , connected by a four - residue type ii 
 -turn . the model of max1 peptide based on the -arch structure of 
 a was examined ( figure 1c and d ) by applying md simulations to the self - assembled 
 peptides . as one can see from figure 1e , after 
 simulations of 26 ns , the self - assembled -arch structure max1 
 is unstable due to the loss of hydrogen bond interactions along the 
 fibril axis ( figure 1e ) . we therefore conclude 
 that the folded state of max1 peptide is not a -arch structure . previously , it was suggested that the max1 peptide self - assembles 
 to form fibrils that cross - link through branch points . each fibril is composed of a bilayer of hairpins 
 that hydrogen - bond along the long axis of a given fibril ( figure 1b ) . we investigated four possible arrangements of 
 the -hairpins constituting the fibril : variants m1m4 
 ( figure 2a ) . m1 and m2 , the turn 
 regions in each layer are organized in the same direction . in the 
 bilayer of m1 , the turn regions are organized in the same direction , 
 while in m2 they are organized in opposite directions along the fibril 
 axis . in models m3 and m4 , the turn regions are organized in opposite 
 directions in each layer . in the bilayer of m3 , the turn regions are 
 organized in the same direction , and in m4 , the turn regions are organized 
 in opposite directions along the fibril axis . we further examined 
 two possible arrangements in the branching point region : variants 
 m5 and m7 and variants m6 and m8 ( figure 2b ) . 
 in models m5 and m7 , the turn regions are organized in the same direction 
 in each layer . in models m6 and m8 , the turn regions are organized 
 in opposite directions in each layer . while in m5 and m6 each of the 
 opposing monolayers illustrate that the hydrophobic residues are exposed 
 to the solvent , in m7 and m8 , the opposing monolayers demonstrate 
 that the hydrophobic residues are not exposed to the solvent . the number 
 of possible organizations at the branching points is large , because 
 the range of angles ( 090 ) at which two layers in the 
 self - assembled peptide can be oriented toward each other is large . illustration 
 of the variant models of the arrangements of the max1 
 hairpins in the gel network morphology . the secondary structure of 
 the hairpins is based on the experimentally designed peptide . the variant models m1m4 
 illustrate arrangement along the peptide fibril growth and in variant 
 models m5m8 show arrangement in the cross - link branch point 
 regions . after 60 ns simulations , all eight 
 self - assembled hairpin models 
 illustrated structurally stable fibrillar cross- structures . interestingly , all m1m4 fibrillar structural models presented 
 small rmsds ( figure 3 ) . while the fibrillar 
 structural models m1 , m3 , and m4 are relatively rigid , the fibrillar 
 model m2 is slightly flexible . the branching models m5m8 are 
 relatively less rigid than the fibrillate models m1m4 . interestingly , models m5 and m6 , that illustrate that the hydrophobic residues are 
 exposed to the solvent , showed relatively large rmsd values ( 2 
  ) compared with the rmsd values of models m7 and m8 ( 1.2 
  ) where the hydrophobic residues are not exposed to the solvent . the rmsd values of 2  are in the range observed in protein structures . 
 in summary , we propose that the arrangements in branching point regions 
 in which the hydrophobic residues are not exposed to the solvent are 
 relatively flexible compared to the fibrillar models and present higher 
 rigidity than the arrangements in the branching point region in which 
 the hydrophobic residues are exposed to the solvent . rmsd values along the 
 md simulations indicating that the fibrillar 
 models are relatively more rigid than the branching models . the high structural stabilities 
 of the fibrillar models m1m4 
 are due to the well protected backbone hydrogen bond networks that 
 are shielded from the solvent . the lysine - rich surface in the fibrillar 
 models is highly charged , while the hydrocarbon side chain of the 
 lysine residues provides a hydrophobic environment for the backbone 
 hydrogen bond networks . to examine this claim , we computed the solvation 
 backbone values for all 20 residues within the -hairpin for 
 each of the fibrillar models m1m4 and the branching models 
 m5m8 ( figure 4 ) . the backbone solvation 
 values for each residue are similar for all eight models , with slight 
 deviations for models m6 and m7 , which illustrate hydrophobic residues 
 that are exposed to the solvent . as one can see from figure 4 , as expected among all 20 residues in the -hairpin , 
 the residues in the c- and n - termini val1 and val20 and the residues 
 in the turn regions pro11 illustrate relatively high solvation values . additionally , one can see an alternative pattern of backbone solvation 
 along the two -strands of the hairpin in line with the alternating 
 sequence of valine and lysine residues . valine residues illustrate 
 relatively small backbone solvation values compared to the lysine 
 residues . at the same time , the backbone solvation values for both 
 valines and lysines are relatively small , indicating the well protected 
 backbone hydrogen bond networks that are shielded from the solvation 
 for all models . average water molecules around each side chain c 
 carbon 
 and backbone atoms ( within 4  ) for models m1m8 . table 1 summarizes the conformational energies 
 of the eight variants of the self - assembled -hairpins computed 
 by the generalized born method with the molecular volume ( gbmv ) method 
 and the populations using monte carlo ( mc ) simulations . among the 
 four possible arrangements of the -hairpins constituting the 
 fibril , variants m1m4 , m2 and m4 have the highest and similar 
 energies and the highest population and m2 is slightly more stable 
 energetically than m4 and dramatically more stable than the other 
 models m1 and m3 . among the possible m5m8 arrangements in 
 the branching point region , variants m6 and m8 are dramatically conformational energies were computed 
 using the gbmv calculations ( refs ( 31 and 32 ) ) . the standard deviation of the energy 
 difference is calculated by x1x2 = sqrt[1/n1 + 2/n2 ] , where x1 and x2 are the means of 
 two samplings and n1 and n2 are the sizes of the sampling ( 500 ) . we therefore suggest that these 
 constructed variant models may 
 provide insight into the mechanisms of the self - assembly of the -hairpins 
 within the hydrogel network s morphology . -hairpins 
 self - assemble to form polymorphic arrangements with a preference toward 
 arrangement along the fibril axis and a preference toward arrangement 
 within the branching point regions . while along the fibril axis the 
 preferred self - assembling occurs when the turn regions oriented in 
 the same directions in each layer and in opposite directions in the 
 bilayer ( e.g. , model m2 ) , within the branching point regions , preferred 
 self - assembling occurs when the turn regions are organized in opposite 
 directions in each layer ( e.g. , models m6 and m8 ) . the persistence lengths of the self - assembled 
 fibril of max1 hydrogels were previously estimated from rheological 
 experiments to be 55 nm . the interactions 
 that control the self - assembly along the fibril bilayer include electrostatic 
 and hydrophobic interactions , and hydrogen bonding between individual 
 -hairpins . electrostatic frustration 
 may affect the organization and persistence length of the assembly 
 of the peptide . to test the effect of electrostatic frustration on 
 the persistence length along the fibril growth of the 16 -hairpins , 
 pairs of -hairpins were removed from the most stable model 
 m2 , that is , 14 -hairpins and a dimer of -hairpins . the total energies of m2 and its small -hairpin pair  fragments  
 were computed with the gbmv method . figure 5 demonstrates the total energies of m2 and its  fragment  
 pairs . energetically , short pairs of the self - assembled hairpins are 
 more favored than the longest self - assembled hairpin , indicating that 
 electrostatic repulsion might overcome hydrogen bonding and hydrophobic 
 interactions permitting further fibril elongation . reveals that the preferred size is between 6 and 10 hairpins ( figure 5c ) . figure 5b illustrates 
 a similar scenario ; the sum of the conformational energies of three 
 pairs of m2  fragments  is less than the conformational 
 energy of the 16 . therefore , the electrostatic frustration disfavors 
 long - axis fibril growth and it is more likely that short persistence 
 lengths are formed , suggesting that the large numbers of cross - links 
 in the network morphology is due to the preference of short persistence 
 lengths . therefore , the shorter persistence lengths may contribute 
 to a stiffer gel material , since the fibrillar structural models are 
 relatively more rigid ( figure 3 ) . sum of energies 
 of self - assembled short persistence lengths and 
 the energy of model m2 that consists of 16 monomers . parts a and b 
 demonstrate that short persistence lengths along the fibril s 
 growth are energetically more favored than the longer fibril ( consisting 
 of 16 monomers ) . as seen in part b , the most favored short persistence 
 lengths for model m2 are octamers and two tetramers . ( c ) the energy 
 gap between the self - assembled model m2 and the self - assembled short 
 persistence length . in addition to the 
 bilayer and the interfibril cross - linking , i.e. , the branch points 
 within the network , it has also been suggested that , at a sufficiently 
 high hairpin concentration , entanglements of the fibrils may also 
 contribute to the mechanical rigidity of the gel . our simulations demonstrate that the short persistence 
 length of the fibrils and interfibril cross - linking strongly contribute 
 to the mechanical rigidity of the fibril . to test the hypothesis that 
 the entanglements of the fibrils also contribute to the mechanical 
 rigidity of the gel , we simulated two self - assembled fibrils that 
 are in close and far proximity from each other ( figure 6a ) . to this end the 
 simulations illustrate that electrostatic repulsions of the lysines 
 between the two fibrils prevent the formation of fibril entanglements . the strong electrostatic repulsions lead to the  breaking  
 of one fibril , reflecting that fibril entanglements can not be achieved 
 when two lysine - rich surfaces are in contact ( figure 6b ) . since it has been proposed that the formation of the entanglements 
 of the fibrils may occur at high concentrations of salt ions , we increased 
 the concentrations of the counterions in the simulations while keeping 
 the system neutralized . interestingly , the simulations at high counterion 
 concentrations illustrated a similar scenario of electrostatic repulsions 
 of the lysines that prevent the formation of the fibril entanglements . we conclude that the electrostatic repulsions of the lysines within 
 the fibrils disfavor the formation of entanglements and therefore 
 help to define the percolated nature of the network . in the network morphology , while the interfibril cross - linking contributes to the 
 material s mechanical rigidity , it is unlikely that the fibrils 
 form entanglements . this conclusion and our results that ( 1 ) max1 
 prefers to have short fibrils and ( 2 ) branched models are more stable 
 than a long max1 fibril point to a cross - linking mechanism for max1 
 hydrogel ( figure 6c ) . we suggest that the max1 
 hydrogel cross - linking is not caused by  imperfection  
 or entanglements of max1 fibril ; rather , the cross - linking state is 
 one of the low energy and stable polymorphic states of max1 peptide 
 ensembles . max1 hydrogel can become fluidic under shear stress and immediately 
 resume its gel state when the shear stress is relieved . in our mechanism , shear stress provides the energy to reach the available short fibrillar 
 structures and thus yield a fluidic hydrogel . when the shear energy 
 disappears , the cross - linking state again becomes more populated . the entanglement mechanism can explain the fast restoration of the 
 gel state immediately after the shear stress stops . our mechanism 
 does not require converting all branching states to short fibrillar 
 structures ; it suffices to provide enough energy to break a large 
 gel domain into a smaller one . consistently , experimental works have 
 shown that random orientation of fibrillar structures does not change 
 under shear stress . our mechanism also 
 implies that stronger hydrophobic interactions can increase the hydrogel 
 mechanical stiffness , since the cross - linking is still provided by 
 hydrophobic surfaces rather than entanglement through lysine - rich 
 surface contact . in support of this , recent experiments have shown 
 that , after the valine residues of max1 were replaced by the more 
 hydrophobic isoleucines , the resulting gels displayed higher mechanical 
 stiffness . a proposed cross - link 
 mechanism of max1 peptide hydrogel . ( a ) initial 
 structure of two max1 fibrils that are contacted with 90 between 
 them . ( b ) simulated structure of the two contacted max1 fibrils demonstrating 
 that the strong electrostatic repulsion between the lysine - rich surfaces 
 does not allow two stable max1 fibrils to form an entangled complex . ( c ) shear forces provide energy to flow and therefore yield for structural 
 transitions . under static conditions , the branching structures of 
 the max1 peptide assembly are more favored and thus provide cross - linking 
 of the hydrogel . however , the shear stress provides energy flow , leading 
 to short fibrillar structures and therefore yields to a fluidic hydrogel . max1 
 undergoes triggered self - assembly at the nanoscale to form 
 a physically cross - linked network of fibrils with a defined cross 
 section . the folded state of 
 max1 is characterized by a type ii -turn ( vppt ) , which connects two amphiphilic -strands 
 of alternating lysine and valine residues , resulting in a hairpin 
 with one hydrophilic , lysine - rich face and one hydrophobic , valine - rich 
 face . this conformation rapidly self - assembles 
 following an external stimulus , yielding a mechanically rigid hydrogel . how the hairpins self - assemble and how the branch points are formed 
 are elusive . to understand the structural features that contribute 
 to the network s morphology and the material s mechanical 
 rigidity of the gel , it is necessary to investigate the structure 
 of the network morphology at the molecular level . recently , the morphologies 
 of the self - assembly of amphiphilic -sheet peptides into various 
 organizations have been investigated at high resolution . herein , using all - atom molecular dynamics 
 ( md ) simulations in explicit 
 solvent , we investigated the network morphology of the hairpins in 
 the fibril s growth domains and at the branch points . the stable 
 variant models of the self - assembled -hairpins were based on 
 the secondary structure which has been designed by schneider and co - workers . overall , our study provides insight into the molecular network morphology 
 of the hairpins in the gel state . the preferred conformation of the 
 max1 peptide is the -hairpin structure , rather than the amyloid - like 
 -arch structure . it is interesting to note that there is similar 
 temperature sensitivity between max1 peptide gel formation and some 
 amyloid formations . because hydrophobic interactions have higher contributions 
 at higher temperatures , they can trigger 
 the formation of the max1 hydrogel . similarly , tau protein amyloids 
 also form at high temperature which can be reversed to small oligomers 
 at low temperature . however , there is 
 an important difference between the temperature sensitivities of the 
 monomer conformation of max1 peptide and tau protein . with increasing 
 temperature , the max1 peptide monomer changes from a random conformation 
 into a -hairpin . on the other hand , tau peptides k19 and k18 
 present metastable secondary structure states ( both -strand and -helix ) at room temperature , and 
 the -strand percentage decreases with increasing temperature . 
 for amyloids , the rate limiting step of self - assembly depends on the 
 nucleus size . thus , the preferred hydrophobic 
 interactions at higher temperatures accelerate the nucleus formation 
 of tau oligomer . while it is possible that formation of the max1 hydrogel 
 is also limited by the nucleus size , the monomeric folding into the 
 -hairpin conformation could be a prerequisite for the formation 
 of the max1 hydrogel nucleus . first , simulations 
 of the hairpins exhibit polymorphic packing of hairpins along the 
 long fibrillar axis and within the branch point regions of the network . 
 our computations suggest a slight preference for turn regions of neighboring 
 hairpins in the bilayer to be organized in opposing directions , as 
 demonstrated by the variant model m2 . second , short persistence lengths 
 along the fibril growth indicate that packing of hairpins within the 
 branch points is preferred over packing along the fibril long axis . electrostatic frustration disfavors long - axis fibril growth ; in the 
 network morphology , it is thus more likely that short persistence 
 lengths are formed . these observations indicate that both the short 
 persistence and the large number of cross - linked branch points may 
 be largely responsible for contributing to the material s mechanical 
 rigidity . a network morphology that is comprised of 
 a large number of branch points and fibrils of shorter persistence 
 lengths leads to a stiffer material . our results indicate that small 
 sizes of self - assembled peptides , i.e. , short persistence lengths 
 along the fibril growth , are energetically preferred over longer fibril 
 sizes . this indicates that the rate limiting step for formation of 
 the hydrogel depends on the nucleus size . finally , electrostatic repulsions 
 between fibrils due to the hydrophilic lysine - rich face disfavor the 
 formation of fibril entanglements and consequently assist in defining 
 the percolated nature of the network morphology . in summary , 
 we confirmed that the building block of max1 hydrogel 
 is a -hairpin structure , not an amyloid - like -arch structure . the self - assembled -hairpin structure of max1 illustrates a 
 well - packed cross- structure . recent md simulations have demonstrated 
 cross- structures in a small collection of peptide molecules . our md simulations and energy estimation presented a polymorphic 
 energy landscape of the max1 peptide assembly , clarifying the mechanism 
 of structural transition in the hydrogel ( figure 6c ) . it was hypothesized that the max1 hydrogel cross - linking 
 is due to imperfections of fibrils . herein , we examined this hypothesis 
 and found that branching structures are more stable than long fibrillar 
 structures . finally , under static conditions , the preferred branching 
 structures of the max1 peptide assembly provide the cross - linking 
 of the hydrogel . however , shear stress provides the energy to convert 
 some branching states into short fibrillar structures , thereby breaking 
 large gel domains into smaller ones and yielding a fluidic hydrogel .
hydrogels are proving to be an excellent 
 class of materials for 
 biomedical applications . 
 the molecular self - assembly of designed max1 
 -hairpin peptides into fibrillar networks has emerged as a 
 novel route to form responsive hydrogels . herein , computational modeling 
 techniques are used to investigate the relative arrangements of individual 
 hairpins within the fibrils that constitute the gel . 
 the modeling 
 provides insight into the morphology of the fibril network , which 
 defines the gel s mechanical properties . 
 our study suggests 
 polymorphic arrangements of the hairpins within the fibrils ; however , 
 the relative populations and the relative conformational energies 
 of the polymorphic arrangements show a preference toward an arrangement 
 of hairpins where their turn regions are not capable of forming intermolecular 
 interaction . 
 repulsive intramolecular electrostatic interactions appear 
 to dictate the formation of fibrils with shorter , rather than longer , 
 persistent lengths . 
 these repulsive intramolecular interactions also 
 disfavor the formation of fibril entanglements . 
 taken together , the 
 modeling predicts that max1 forms a network containing a large number 
 of branch points , a network morphology supported by the formation 
 of short fibril segments . 
 we posit that , under static conditions , 
 the preferred branched structures of the max1 peptide assembly result 
 in a cross - linked hydrogel organization . at the same time 
 , the shear 
 stress leads to short fibrillar structures , thus fluidic hydrogel 
 states .