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4(%3)3 - Ecole nationale supérieure de chimie de Montpellier

4(%3)3 - Ecole nationale supérieure de chimie de Montpellier

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3. TRANSLOCATION ACROSS A SELF-HEALING MEMBRANETranslocation of matter across biological membranes is one of the most crucial processes in nature,being essential for both <strong>de</strong>livery and signaling purposes 1 . Due to recent use of nanoparticles aspotential drug carriers 2,3 , sub-cellular sensors 4,5 and imagers 6,7 , nanoinjectors 8 , and gene carriers 9 , theirtrafficking across lipid membranes has been studied extensively for better un<strong>de</strong>rstanding of theprocess 10-13 . Translocation has been in<strong>de</strong>ntified to happen either by a “direct penetration” (diffusion)process in which a nanoparticle or nano-object diffuses through cellular membrane un<strong>de</strong>r the effect ofan external force or by a much more prevalent “receptor mediated endocytosis” 14-16 process whichinvolves internalization of the matter via three steps 17-19 : First being the adsorption of nanoparticle ornano-object over the surface of the cellular membrane via functional groups, second being theirwrapping or engulfing by the membrane and third being the “pinching-off” of the lipid-particle complexfrom the membrane 20 . Usually, the direct mo<strong>de</strong> of translocation (diffusion) is consi<strong>de</strong>red less attractivefrom practical applications point of view as compared to endocytosis process since the former involvesthe application of an external force 8,12 and in most cases the <strong>de</strong>licate membrane structure is disrupted bythis force induced translocation. In recent works, although novel polymer architectures like<strong>de</strong>ndrimers 21-23 have been used to create pore across the membrane across their passage way tofacilitate the diffusion process but the permanent nature of the pores has <strong>de</strong>trimental effect on themembrane which in worst case can even lead to its complete <strong>de</strong>struction 24 and consequently cell <strong>de</strong>ath.The problem of permanent pore formation in the membrane and its structural failure can becircumvented if the membrane is able to close the created pores by itself while the particle moves acrossit.In this chapter we have investigated the above scenario by carrying out the translocation ofdifferent nano-objects having different geometry, size and surface characteristics across a self-healingmembrane (Figure – 3.1). We recall that this self-healing membrane 25 discussed in the previous chapter,is essentially a 3-dimensional network of a triblock copolymer micelles held together dynamically viacopolymer chains acting as bridges. While the interstitial space between the spherical constituent75

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