Polypeptide Composition and Topology Affect Hydrogelation of Star-Shaped Poly(L-lysine)-Based Amphiphilic Copolypeptides

Abstract

In this research, we studied the effect of polypeptide composition and topology on the hydrogelation of star-shaped block copolypeptides based on hydrophilic, coil poly(_L-lysine)₂₀ (s-PLL₂₀) tethered with a hydrophobic, sheet-like polypeptide segment, which is poly(_L-phenylalanine) (PPhe), poly(_L-leucine) (PLeu), poly(_L-valine) (PVal) or poly(_L-alanine) (PAla) with a degree of polymerization (DP) about 5. We found that the PPhe, PLeu, and PVal segments are good hydrogelators to promote hydrogelation. The hydrogelation and hydrogel mechanical properties depend on the arm number and hydrophobic polypeptide segment, which are dictated by the amphiphilic balance between polypeptide blocks and the hydrophobic interactions/hydrogen bonding exerted by the hydrophobic polypeptide segment. The star-shaped topology could facilitate their hydrogelation due to the branching chains serving as multiple interacting depots between hydrophobic polypeptide segments. The 6-armed diblock copolypeptides have better hydrogelation ability than 3-armed ones and s-PLL-b-PPhe exhibits better hydrogelation ability than s-PLL-b-PVal and s-PLL-b-PLeu due to the additional cation-π and π-π interactions. This study highlights that polypeptide composition and topology could be additional parameters to manipulate polypeptide hydrogelation.

Keywords: chain conformation; hydrogels; polymer topology; polypeptide; self-assembly.

Scheme 1

The representative scheme for synthesis of star-shaped s-PLL-b-PY diblock copolypeptides and the formation of hydrogels.

Figure 1

¹H NMR spectra of (a) 3s-PZLL₂₂ in TFA-d₁, (b) 3s-PZLL₂₂-b-PLeu_5.5 in TFA-d₁, and (c) 3s-PLL₂₂-b-PLeu_5.5 in DMSO-d₆.

Figure 2

(a) CD and (b) FTIR spectra of star-shaped s-PLL-b-PY diblock copolypeptides. The polypeptide concentration was 0.1 mg mL⁻¹ for CD analysis.

Figure 3

SEM images of freeze-dried (a) 3s-PLL₂₂-b-PLeu_5.5 (8.0 wt%), (b) 6s-PLL₂₁-b-PLeu_4.4 (5.0 wt%), (c) 3s-PLL₂₂-b-PVal_5.1 (8.0 wt%), (d) 6s-PLL₂₁-b-PVal₅ (5.0 wt%), (e) 3s-PLL₂₂-b-PPhe_6.3 (5.0 wt%) and (f) 6s-PLL₂₁-b-PPhe_5.3 (5.0 wt%) hydrogel samples.

Figure 4

(a) Storage modulus G′ (solid symbols) and loss modulus G′′ (open symbols) of 6s-PLL₂₁-b-PPhe_5.3 (5.0 wt%), 3s-PLL₂₂-b-PPhe_6.3 (5.0 wt%), 6s-PLL₂₁-b-PLeu_4.4 (5.0 wt%), 3s-PLL₂₂-b-PLeu_5.5 (8.0 wt%), 6s-PLL₂₁-b-PVal₅ (5.0 wt%), and 3s-PLL₂₂-b-PVal_5.1 (8.0 wt%) hydrogels as a function of angular frequency at strain = 0.1%; (b) strain sweeps for the same samples at frequency = 1.0 rad/s.

Figure 5

Storage modulus G′ as a function of time for 6s-PLL₂₁-b-PPhe_5.3 (5.0 wt%), 3s-PLL₂₂-b-PPhe_6.3 (5.0 wt%), 6s-PLL₂₁-b-PLeu_4.4 (5.0 wt%), 3s-PLL₂₂-b-PLeu_5.5 (8.0 wt%), 6s-PLL₂₁-b-PVal₅ (5.0 wt%), and 3s-PLL₂₂-b-PVal_5.1 (8.0 wt%) hydrogel samples. At 100 s, the gel structure was broken down at a constant strain of 100% and an angular frequency of 1.0 rad/s by applying nonlinear large-amplitude oscillations. Then, the mechanical strength recovery of the hydrogel samples was monitored at a constant strain of 1% and an angular frequency of 1.0 rad/s.

Figure 6

SAXS profiles of (a) 3s-PLL₂₂-b-PPhe_6.3, (b) 6s-PLL₂₁-b-PPhe_5.3, (c) 3s-PLL₂₂-b-PLeu_5.5, and (d) 6s-PLL₂₁-b-PLeu_4.4 sol and gel solutions at different polypeptide concentrations in DI water.