Insulin adsorption on functionalized silica surfaces: an accelerated molecular dynamics study


We study the influence of surface functionalization of a silica surface on insulin adsorption using accelerated molecular dynamics simulation. Three different functional groups are studied, CH3, OH, and COOH. Due to the partial charges of these groups, the surface polarity of silica is strongly altered. We find that the adsorption energies of insulin change in agreement with the decreasing surface polarity. Conformational changes in the adsorbed protein and the magnitude of the molecular dipole moment in the adsorbed state are consistent with this result. We conclude that protein adsorption on functionalized polar surfaces is governed by the induced changes in surface polarity.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3
Fig. 4


  1. 1.

    Andronescu E, Grumezescu AM (eds) (2017) Nanostructures for drug delivery. Elsevier, Amsterdam

  2. 2.

    Kotzabasaki M, Galdadas I, Tylianakis E, Klontzas E, Cournia Z, Froudakis GE (2017) Multiscale simulations reveal IRMOF-74-III as a potent drug carrier for gemcitabine delivery. J Mater Chem B 5:3277–3282

    CAS  Article  Google Scholar 

  3. 3.

    Coelho JF, Ferreira PC, Alves P, Cordeiro R, Fonseca AC, Góis JR, Gil MH (2010) Drug delivery systems: Advanced technologies potentially applicable in personalized treatments. EPMA J 1:164–209

    Article  Google Scholar 

  4. 4.

    Kwon S, Singh RK, Perez RA, Neel EAA, Kim H-W, Chrzanowski W (2013) Silica-based mesoporous nanoparticles for controlled drug delivery. J Tissue Eng 4:2041731413503357

    Article  Google Scholar 

  5. 5.

    Desai TA, West T, Cohen M, Boiarski T, Rampersaud A (2004) Nanoporous microsystems for islet cell replacement. Adv Drug Deliv Rev 56:1661–1673

    CAS  Article  Google Scholar 

  6. 6.

    Sekigami T, Shimoda S, Nishida K, Matsuo Y, Ichimori S, Ichinose K, Shichiri M, Sakakida M, Araki E (2004) Comparison between closed-loop portal and peripheral venous insulin delivery systems for an artificial endocrine pancreas. J Artif Organs 7:91–100

    CAS  Article  Google Scholar 

  7. 7.

    Geetha S (2014) Artificial drug delivery system for diabetes. Indian J Sci Technol 7:58–61

    Google Scholar 

  8. 8.

    Matteucci E, Giampietro O, Covolan V, Giustarini D, Fanti P, Rossi R (2015) Insulin administration: present strategies and future directions for a noninvasive (possibly more physiological) delivery. Drug Des Devel Ther 9:3109–3118

    CAS  Article  Google Scholar 

  9. 9.

    Zahid N, Taylor KMG, Gill H, Maguire F, Shulman R (2008) Adsorption of insulin onto infusion sets used in adult intensive care unit and neonatal care settings. Diabet Res Clin Pract 80:e11–e13

    CAS  Article  Google Scholar 

  10. 10.

    Mollmann SH, Bukrinsky JT, Frokjaer S, Elofsson U (2005) Adsorption of human insulin and AspB28 insulin on a PTFE-like surface. J Colloid Interface Sci 286:28–35

    CAS  Article  Google Scholar 

  11. 11.

    Mollmann SH, Jorgensen L, Bukrinsky JT, Elofsson U, Norde W, Frokjaer S (2006) Interfacial adsorption of insulin conformational changes and reversibility of adsorption. Eur J Pharm Sci 27:194

    CAS  Article  Google Scholar 

  12. 12.

    Pikulski M, Gorski W (2000) Iridium-based electrocatalytic systems for the determination of insulin. Anal Chem 72:2696–2702

    CAS  Article  Google Scholar 

  13. 13.

    Kaur A, Verma N (2012) Electrochemical biosensor for monitoring insulin in normal individuals and diabetic mellitus patients. Euro J Exp Bio 2:389–395

    CAS  Google Scholar 

  14. 14.

    Wu Y, Chen C, Liu S (2009) Enzyme-functionalized silica nanoparticles as sensitive labels in biosensing. Anal Chem 81: 1600–1607

    CAS  Article  Google Scholar 

  15. 15.

    Patil YB, Toti US, Khdair A, Ma L, Panyam J (2009) Single-step surface functionalization of polymeric nanoparticles for targeted drug delivery. Biomaterials 30:859–866

    CAS  Article  Google Scholar 

  16. 16.

    Wang H, Agarwal S, Zhao S, Yu J, Lu X, He X (2016a) Combined cancer therapy with hyaluronan-decorated fullerene-silica multifunctional nanoparticles to target cancer stem-like cells. Biomaterials 97:62–73

  17. 17.

    Wang Y, Li P, Tran TT-D, Zhang J, Kong L (2016) Manufacturing techniques and surface engineering of polymer based nanoparticles for targeted drug delivery to cancer. Nanomaterials 6:26

    Article  Google Scholar 

  18. 18.

    Ratner BD, Bryant SJ (2004) Biomaterials: where we have been and where we are going. Annu Rev Biomed Eng 6:41

    CAS  Article  Google Scholar 

  19. 19.

    Nakanishi K, Sakiyama T, Imamura K (2001) On the adsorption of proteins on solid surfaces, a common but very complicated phenomenon. J Biosci Bioeng 91:233–244

    CAS  Article  Google Scholar 

  20. 20.

    Poger D, Mark AE (2013) Study of proteins and peptides at interfaces by molecular dynamics simulation techniques. In: Ruso JM, Pineiro A (eds) Proteins in solution and at interfaces: methods and applications in biotechnology and materials science. Wiley, Hoboken, p Ch 14, 291

  21. 21.

    Kubiak-Ossowska K, Mulheran PA (2010) What governs protein adsorption and immobilization at a charged solid surface? Langmuir 26:7690

    CAS  Article  Google Scholar 

  22. 22.

    Kubiak-Ossowska K, Mulheran PA, Nowak W (2014) Fibronectin module FNIII9 adsorption at contrasting solid model surfaces studied by atomistic molecular dynamics. J Phys Chem B 118:9900–9908

    CAS  Article  Google Scholar 

  23. 23.

    Kubiak-Ossowska K, Cwieka M, Kaczynska A, Jachimska B, Mulheran PA (2015) Lysozyme adsorption at a silica surface using simulation and experiment: effects of pH on protein layer structure. Phys Chem Chem Phys 17:24070

    CAS  Article  Google Scholar 

  24. 24.

    Tosaka R, Yamamoto H, Ohdomari I, Watanabe T (2010) Adsorption mechanism of ribosomal protein L2 onto a silica surface: a molecular dynamics simulation study. Langmuir 26:9950–9955

    CAS  Article  Google Scholar 

  25. 25.

    Buijs J, Costa Vera C, Ayala E, Steensma E, Hakansson P, Oscarsson S (1999) Conformational stability of adsorbed insulin studied with mass spectrometry and hydrogen exchange. Anal Chem 71:3219

    CAS  Article  Google Scholar 

  26. 26.

    Jorgensen L, Bennedsen P, Vrϕ nning Hoffmann S, Krogh RL, Pinholt C, Groenning M, Hostrup S, Bukrinsky JT (2011) Adsorption of insulin with varying self-association profiles to a solid teflon surface - influence on protein structure, fibrillation tendency and thermal stability. Eur J Pharm Sci 42:509

  27. 27.

    Ademovic Z, Salber J, Klee D (2015) Interaction of insulin and polymer surface investigated by surface-MALDI-TOF-mass spectrometry. Croat Chem Acta 88:213

    CAS  Article  Google Scholar 

  28. 28.

    Nejad MA, Mücksch C, Urbassek HM (2017) Insulin adsorption on crystalline SiO2: Comparison between polar and nonpolar surfaces using accelerated molecular-dynamics simulations. Chem Phys Lett 670:77–83

    CAS  Article  Google Scholar 

  29. 29.

    Zhou J, Chen S, Jiang S (2003) Orientation of adsorbed antibodies on charged surfaces by computer simulation based on a united-residue model. Langmuir 19:3472–3478

    CAS  Article  Google Scholar 

  30. 30.

    Peng C, Liu J, Zhao D, Zhou J (2014) Adsorption of hydrophobin on different self-assembled monolayers: the role of the hydrophobic dipole and the electric dipole. Langmuir 30:11401–11411

    CAS  Article  Google Scholar 

  31. 31.

    Petrash S, Liebmann-Vinson A, Foster MD, Lander LM, Brittain WJ, Majkrzak CF (1997) Neutron and X-ray reflectivity studies of human serum albumin adsorption onto functionalized surfaces of self-assembled monolayers. Biotechnol Prog 13:635–639

    CAS  Article  Google Scholar 

  32. 32.

    Ombelli M, Costello LB, Meng QC, Composto RJ, Eckmann DM (2005) Competitive adsorption of plasma proteins on polysaccharide-modified silicon surfaces. Mater Res Soc Symp Proc 845:AA8.6.1

    Google Scholar 

  33. 33.

    Mauri S, Volk M, Byard S, Berchtold H, Arnolds H (2015) Stabilization of insulin by adsorption on a hydrophobic silane self-assembled monolayer. Langmuir 31:8892–8900

    CAS  Article  Google Scholar 

  34. 34.

    Khanniche S, Mathieu D, Pereira F, Hairault L (2017) Atomistic models of hydroxylated, ethoxylated and methylated silica surfaces and nitrogen adsorption isotherms: a molecular dynamics approach. Microporous Mesoporous Mater 250:158–169

    CAS  Article  Google Scholar 

  35. 35.

    Corno M, Delle Piane M, Monti S, Moreno-Couranjou M, Choquet P, Ugliengo P (2015) Computational study of acidic and basic functionalized crystalline silica surfaces as a model for biomaterial interfaces. Langmuir 31:6321–6331

    CAS  Article  Google Scholar 

  36. 36.

    Rigo VA, de Lara LS, Miranda CR (2014) Energetics of formation and hydration of functionalized silica nanoparticles: an atomistic computational study. Appl Surf Sci 292:742–749

    CAS  Article  Google Scholar 

  37. 37.

    de Lara LS, Rigo VA, Miranda CR (2015) The stability and interfacial properties of functionalized silica nanoparticles dispersed in brine studied by molecular dynamics. Eur Phys J B 88:261

    Article  Google Scholar 

  38. 38.

    de Lara LS, Rigo VA, Miranda CR (2016) Functionalized silica nanoparticles within multicomponent oil/brine interfaces: a study in molecular dynamics. J Phys Chem C 120:6787–6795

    Article  Google Scholar 

  39. 39.

    Hamelberg D, Mongan J, McCammon JA (2004) Accelerated molecular dynamics: a promising and efficient simulation method for biomolecules. J Chem Phys 120:11919

    CAS  Article  Google Scholar 

  40. 40.

    Mücksch C, Urbassek HM (2013) Enhancing protein adsorption simulations by using accelerated molecular dynamics. PLoS One 8:e64883

    Article  Google Scholar 

  41. 41.

    Cruz-Chu ER, Aksimentiev A, Schulten K (2006) Water-silica force field for simulating nanodevices. J Phys Chem B 110:21497

    CAS  Article  Google Scholar 

  42. 42.

    Patwardhan SV, Emami FS, Berry RJ, Jones SE, Naik RR, Deschaume O, Heinz H, Perry CC (2012) Chemistry of aqueous silica nanoparticle surfaces and the mechanism of selective peptide adsorption. J Am Chem Soc 134:6244–6256

    CAS  Article  Google Scholar 

  43. 43.

    Mulheran PA, Connell DJ, Kubiak-Ossowska K (2016) Steering protein adsorption at charged surfaces: electric fields and ionic screening. RSC Adv 6:73709–73716

    CAS  Article  Google Scholar 

  44. 44.

    Kubiak-Ossowska K, Tokarczyk K, Jachimska B, Mulheran PA (2017) Bovine serum albumin adsorption at a silica surface explored by simulation and experiment. J Phys Chem B 121:3975–3986

    CAS  Article  Google Scholar 

  45. 45.

    Rozanska X, Delbecq F, Sautet P (2010) Reconstruction and stability of β-cristobalite 001, 101, and 111 surfaces during dehydroxylation. Phys Chem Chem Phys 12:14930–14940

    CAS  Article  Google Scholar 

  46. 46.

    Vanommeslaeghe K, Hatcher E, Acharya C, Kundu S, Zhong S, Shim J, Darian E, Guvench O, Lopes P, Vorobyov I et al (2010) CHARMM general force field: a force field for drug-like molecules compatible with the CHARMM all-atom additive biological force fields. Comput Chem 31:671

    CAS  Google Scholar 

  47. 47.

    MacKerrell AD Jr, Bashford D, Bellott M, Dunbrack RL Jr, Evanseck JD, Field MJ, Fischer S, Gao J, Guo H, Ha S et al (1998) All-atom empirical potential for molecular modeling and dynamics studies of proteins. J Phys Chem B 102:3586–3616

    Article  Google Scholar 

  48. 48.

    Ionescu C-M, Sehnal D, Falginella FL, Pant P, Pravda L, Bouchal T, Svobodová Vařeková R, Geidl S, Koča J (2015) AtomicChargeCalculator: interactive web-based calculation of atomic charges in large biomolecular complexes and drug-like molecules. J Cheminf 7:50

    Article  Google Scholar 

  49. 49.

    Baker EN, Blundell TL, Cutfield JF, Cutfield SM, Dodson EJ, Dodson GG, Hodgkin DMC, Hubbard RE, Isaacs NW, Reynolds CD et al (1988) The structure of 2Zn pig insulin crystals at 1.5 Å resolution. Philos Trans R Soc london, Ser B 319:369

    CAS  Article  Google Scholar 

  50. 50.

    Jorgensen WL, Chandrasekhar J, Madura JD, Impey RW, Klein ML (1983) Comparison of simple potential functions for simulating liquid water. J Chem Phys 79:926

    CAS  Article  Google Scholar 

  51. 51.

    Phillips JC, Braun R, Wang W, Gumbart J, Tajkhorshid E, Villa E, Chipot C, Skeel RD, Kale L, Schulten K (2005) Scalable molecular dynamics with NAMD. J Comp Chem 26:1781

    CAS  Article  Google Scholar 

  52. 52.

    Ryckaert JP, Ciccotti G, Berendsen HJC (1977) Numerical integration of the cartesian equations of motion of a system with constraints: molecular dynamics of n-alkanes. J Comput Phys 23:327

    CAS  Article  Google Scholar 

  53. 53.

    Darden T, York D, Pedersen L (1993) Particle mesh Ewald: an N log(N) method for Ewald sums in large systems. J Chem Phys 98:10089

    CAS  Article  Google Scholar 

  54. 54.

    Humphrey W, Dalke A, Schulten K (1996) VMD – Visual Molecular Dynamics. J Mol Graph 14:33–38

    CAS  Article  Google Scholar 

  55. 55.

    Stone J (1998) An Efficient Library for Parallel Ray Tracing and Animation, Masters thesis, Computer Science Department, University of Missouri-Rolla

  56. 56.

    Norde W, Giacomelli CE (1999) Conformational changes in proteins at interfaces: from solution to the interface, and back. Macromol Symp 145:125

    CAS  Article  Google Scholar 

  57. 57.

    Anand G, Sharma S, Dutta AK, Kumar SK, Belfort G (2010) Conformational transitions of adsorbed proteins on surfaces of varying polarity. Langmuir 26:10803–10811

    CAS  Article  Google Scholar 

  58. 58.

    Hartvig RA, van de Weert M, Ostergaard J, Jorgensen L, Jensen H (2011) Protein adsorption at charged surfaces: the role of electrostatic interactions and interfacial charge regulation. Langmuir 27:2634–2643

    CAS  Article  Google Scholar 

  59. 59.

    Frishman D, Argos P (1995) Knowledge-based protein secondary structure assignment. Proteins: Struct Funct Genet 23:566

    CAS  Article  Google Scholar 

Download references


We appreciate the computational resources provided by the compute cluster ‘Elwetritsch’ of the University of Kaiserslautern.

Author information



Corresponding author

Correspondence to Herbert M. Urbassek.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Nejad, M.A., Urbassek, H.M. Insulin adsorption on functionalized silica surfaces: an accelerated molecular dynamics study. J Mol Model 24, 89 (2018).

Download citation


  • Molecular dynamics
  • Protein adsorption
  • Insulin
  • Silica
  • Surface functionalization
  • Electrical dipole