(Bio- and Nano-)

Materials Engineering
Day 03
 Course (Module) Plan

Week Topic Question Set

1 – Tue 9 Feb Hydrophobicity 1
2 – Tue 16 Feb Surface Tension + Thin Films 2
3 – Tue 23 Feb Biomaterials (part 1)
3
4 – Tue 2 Mar Biomaterials (part 2)
5 – Tue 9 Mar Electron Microscopy
4
6 – Tue 16 Mar TEM Visit* (+ intro to Phase Diagrams)
5
7 – Tue 23 Mar Phase Diagrams

 *TEM visit:
 Date TBC, pending equipment setup at Centre for Advanced Microscopy
 Will require some outside of 5-7 pm attendance, further details to come
 Can you think of an
example of biomedical
engineering?
Personal Medical Devices
Bioinformatics
Bioinformatics
The tragic tale of coffee and Kiara
Bioinformatics
Big Data for Big Problems
Bioinformatics
Google knows best
Microfluidic Diagnostics
Nanoparticle Drug Carriers
Tissue Engineering
(Tissue) Engineering = Laziness

“Necessity may be the mother of invention,

but laziness is definitely its father.”
How/why was the first webcam invented?
The Extracellular Matrix (ECM)

Tissue engineering materials

mimic the ECM and provide:

Support:
- A scaffold for new cells

And guidance, by
mimicking properties of
specific healthy tissue:
- Physical
- Morphological
- Chemical
- Biological
“Let’s get down to business”
ECM = Hydrogel + Nanofibres
 Self-Assembling Peptide (SAP)
Hydrogels
Aqueous, pH
Engineering! Biological cue controlled

D
E

Void filling, E
Hydrogel Nanofibrous
controlled stiffness
 Self-Assembling Peptide (SAP)
Hydrogels
Aqueous, pH
Engineering! Biological cue controlled

D
E

Void filling, E
Hydrogel Nanofibrous
controlled stiffness
Minimally Invasive
Chemical vs Physical Gels

permanent chemical bonds reversible physical bonds

Maintain shape under force Flow like water in needle
“Mission accomplished!”
(Peptide) Chemistry 101
 Atomic Motivations

We love
electrons!
We want to
be negative

And we’re
happy as is

We hate electrons! We want to be positive

 pH

[H+]: Square bracket notation

denotes concentration, [H+] means
the amount or concentration of H+.

+
𝑝𝐻 = − log10 ([𝐻 ])
H+
OH-

H2O H2O H2O

H+ H2O OH-
Strong Acids/Bases

One way reaction. Complete

dissociation. All H in the molecule
becomes H+ in the solution, increasing
[H+] and decreasing pH.

HCl → H + + Cl-

NaOH → Na+ + OH-

 Chemical Equilibrium
Two-way reactions

H2O H+ + OH-

a(A) + b(B) c(C) + d(D)

[𝐶]𝑐 [𝐷]𝑑 Equilibrium constant K describes

the chemical equilibrium. As some
𝐾= products or reactants are
[𝐴]𝑎 [𝐵]𝑏 added/removed, the others will
adjust and K will remain constant
Chemical Equilibrium
Two-way reactions

CO2(g) + H2O(l) H2CO3(aq) + 42.1 kJ

Carbonated beverages need dissolved (aq) H2CO3(aq) to

be fizzy

Equilibrium acting to undo the change:

- Pressure: For gases, pressure is a component in the K
formula. Adding pressure favours the side of the
reaction with less pressure (pressure = gas), so favours
the side with fewer gas (g) molecules.
- Heat: Heat does shift the K value, but still in a way to
undo the change. In an exothermic reaction (in which
heat is a product), increasing temperature (adding
heat) shifts K to favour reagents and decreasing
temperature (removing heat) shifts K to favour products.
Therefore, soft drink are best served cold!
Chemical Equilibrium
How could you improve drug yield?

A+B drug + water

Weak Acids/Bases

R-COOH R-COO- + H+

R-NH2 + H2O R-NH3+ + OH-

pKa

- +
R-COOH R-COO + H
+ −
𝐻 [𝑅 − 𝐶𝑂𝑂 ]
𝐾𝑎 =
[𝑅 − 𝐶𝑂𝑂𝐻]

pKa = pH at which equilibrium is 50:50

Who gets the H?

Below pKa pKa Above pKa

- acidic - basic/alkaline
- lots of H+ available - environment lacks H+
- dominant form with H - dominant form without H

more R-COOH ~4 more R-COO-

more R-NH3+ ~10 more R-NH2
SAP Chemistry

D
E

E
 Designing Peptide
Hydrogels via Charge:
Fmoc-DIKVAV
Designing SAPs - DIKVAV

Tuning the amino acid sequence of minimalist peptides to present biological

signals via charge neutralised self assembly
AL Rodriguez, CL Parish, DR Nisbet, RJ Williams
Soft Matter 9 (15), 3915-3919
To H or not to H?

Below pKa At pKa Above pKa

- acidic - basic/alkaline
- lots of H+ available - environment lacks H+
- preferred form with H - preferred form without H

more R-COOH ~4 more R-COO-

more R-NH3+ ~10 more R-NH2
 A Non-Linear Decision

100%

75%
Proportion in Specific Form

50%
COOH
COO-

25%

0%
0 2 4 6 8 10 12 14
pH
 A Non-Linear Decision

100%

75%
Proportion in Specific Form

50%
NH2
NH3+

25%

0%
0 2 4 6 8 10 12 14
pH
 As pH changes, the charges
along the peptide molecules
change. There is a charge
sweet spot at which self-
assembly occurs
 Temperature switch
method for complex
supra-personal structures
of humans

An analogy for the pH-switch method for the formation of supramolecular structures in
peptide molecules
Nice warm day

 Humans are spread out,

enjoying the nice warm
weather
 Dissolved in solution
Too cold, too fast

 Canadian humans all cram

inside a house where it’s
warm
 Undissolved solid
If there are enough warm
bodies

 Penguins stay outside,

forming large groups to
keep warm
 Very long peptide chains
(like real proteins) self-
assemble more easily
Cooling down slowly

 Australian humans stay

outside as the weather
gets cooler and huddle in
small groups around little
outdoor heaters
 Supramolecular peptide
structures (nanofibres),
not really dissolved in
solution, but still existing
and interacting with the
water environment
Designing Peptide
Hydrogels
(more examples)
 We all scream for Lysine!

Tailoring minimalist self-assembling peptides for localized viral vector gene delivery
Alexandra L Rodriguez, Ting-Yi Wang, Kiara F Bruggeman, Rui Li, Richard J Williams, Clare L Parish, David R Nisbet
2016/3/1 Nano research
Designing SAPs - FRGDF
Amino Acid Building Blocks
SAP Hydrogels with a(n
in)side order of drugs!
 BDNF Engraftment

Shear containment of BDNF within

molecular hydrogels promotes human
stem cell engraftment and postinfarction
remodeling in stroke
DR Nisbet, TY Wang, KF Bruggeman, JC
Niclis, FA Somaa, V Penna, CPJ Hunt, Y
Wang, JA Kauhausen, Richard J Williams,
LH Thompson, CL Parish
Advanced Biosystems 2 (9), 1800113
Acknowledgements

Dr. David Nisbet, Australian

National University
Dr. Clare Parish, Florey
Institute of Neuroscience
Dr. Richard Williams, Royal
Melbourne Institute of
Technology
Funding: NHMRC, ARC
Microscopy: AMMRF
The LAB (Laboratory of
Advanced Biomaterials),
Australian National University
Questions?
Closing Notes

 No problem set this week! Question Set 3 posted to wattle next

week, will include some concepts from this week
 Photos of pracs? Please tag @therainbowscientist on Instagram
 Next week: TBD