Engineering a Stable Synaptogenic Extracellular Matrix

Laila Al-Alwan, Markus Hellmund, Rainer Haag, Timothy Kennedy

Abstract

Synapses are specialized sites of asymmetric cell – cell contact that mediate information transfer between neurons and their targets. Many proteins involved in the recruitment, organization and maintenance of synapses have been identified. Surprisingly, synaptic differentiation does not require a biological membrane surface. Instead, synaptic specializations can form quickly at sites of neurite adhesion to microspheres (beads) coated with synaptogenic proteins or even poly-lysine, a synthetic cationic polypeptide, raising the possibility that functional hemi-synaptic connections could be formed onto designer engineered surfaces. Previous studies examining the stability of synapses formed in brain onto poly-lysine coated beads found they were unstable, degraded, and ultimately replaced by a glial scar. Here, we address the capacity of an extreme biomimetic of poly-lysine, PGB50, a dendritic polyglycerol (dPG)-amine soft matter nanoparticle, to enhance synapse formation in long-term cultures of rat cortical neurons. Microbeads coated with PGB50 exhibit substantially enhanced synaptogenesis and synapse stability compared to poly-lysine. We propose that synaptogenic extracellular matrices could be used to engineer synaptogenic electrodes with enhanced neural-compatibility, reducing glial scaring and inflammation, and allowing for bi-directional communication with neurons through the formation of stable of synaptic specializations.

References

  1. Burry RW (1982) Development of apparent presynaptic elements formed in response to polylysine coated surfaces. Brain research 247:1-16.
  2. Burry RW (1983) Postnatal rat neurons form apparent presynaptic elements on polylysine-coated beads in vivo. Brain research 278:236-239.
  3. Burry RW (1985) Protein synthesis requirement for the formation of synaptic elements. Brain research 344:109-119.
  4. Goldman JS, Ashour MA, Magdesian MH, Tritsch NX, Harris SN, Christofi N, Chemali R, Stern YE, Thompson-Steckel G, Gris P, Glasgow SD, Grutter P, Bouchard JF, Ruthazer ES, Stellwagen D, Kennedy TE (2013) Netrin-1 promotes excitatory synaptogenesis between cortical neurons by initiating synapse assembly. The Journal of neuroscience : the official journal of the Society for Neuroscience 33:17278- 17289.
  5. Gopalakrishnan G, Thostrup P, Rouiller I, Lucido AL, Belkaid W, Colman DR, Lennox RB (2010) Lipid bilayer membrane-triggered presynaptic vesicle assembly. ACS chemical neuroscience 1:86-94.
  6. Hellmund M, Achazi K, Neumann F, Thota BN, Ma N, Haag R (2015) Systematic adjustment of charge densities and size of polyglycerol amines reduces cytotoxic effects and enhances cellular uptake. Biomaterials science 3:1459-1465.
  7. Hochberg LR, Bacher D, Jarosiewicz B, Masse NY, Simeral JD, Vogel J, Haddadin S, Liu J, Cash SS, van der Smagt P, Donoghue JP (2012) Reach and grasp by people with tetraplegia using a neurally controlled robotic arm. Nature 485:372-375.
  8. Lucido AL, Suarez Sanchez F, Thostrup P, Kwiatkowski AV, Leal-Ortiz S, Gopalakrishnan G, Liazoghli D, Belkaid W, Lennox RB, Grutter P, Garner CC, Colman DR (2009) Rapid assembly of functional presynaptic boutons triggered by adhesive contacts. The Journal of neuroscience : the official journal of the Society for Neuroscience 29:12449-12466.
  9. Suarez F, Thostrup P, Colman D, Grutter P (2013) Dynamics of presynaptic protein recruitment induced by local presentation of artificial adhesive contacts. Developmental neurobiology 73:98-106.
  10. van den Brand R, Heutschi J, Barraud Q, DiGiovanna J, Bartholdi K, Huerlimann M, Friedli L, Vollenweider I, Moraud EM, Duis S, Dominici N, Micera S, Musienko P, Courtine G (2012) Restoring voluntary control of locomotion after paralyzing spinal cord injury. Science 336:1182-1185.
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Paper Citation


in Harvard Style

Al-Alwan L., Hellmund M., Haag R. and Kennedy T. (2016). Engineering a Stable Synaptogenic Extracellular Matrix . In - NEUROTECHNIX, ISBN , pages 0-0


in Bibtex Style

@conference{neurotechnix16,
author={Laila Al-Alwan and Markus Hellmund and Rainer Haag and Timothy Kennedy},
title={Engineering a Stable Synaptogenic Extracellular Matrix},
booktitle={ - NEUROTECHNIX,},
year={2016},
pages={},
publisher={SciTePress},
organization={INSTICC},
doi={},
isbn={},
}


in EndNote Style

TY - CONF
JO - - NEUROTECHNIX,
TI - Engineering a Stable Synaptogenic Extracellular Matrix
SN -
AU - Al-Alwan L.
AU - Hellmund M.
AU - Haag R.
AU - Kennedy T.
PY - 2016
SP - 0
EP - 0
DO -